Expression Of Laminin Receptor Research Articles

Laminin receptor 1 expression in premalignant and malignant squamous lesions of the cervix

ABSTRACT Laminin receptor 1 (LAMR) may have a role in the progression of premalignant squamous epithelial lesions to cervical cancer. Therefore, we aimed to investigate the expression of laminin receptor 1 (LAMR) in normal, premalignant, and malignant tissues of the uterine cervix. Paraffin blocks of 129 specimens with the diagnoses of normal cervical tissue (n = 33), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2 (n = 14), CIN 3 (n = 28), and squamous cell carcinoma (n = 24) were immunohistochemically stained with LAMR antibody and its expression percentage, pattern, and intensity in these tissues were assessed. Compared to the other groups, the nonstaining with LAMR was highest in low grade squamous intraepithelial lesion (LSIL) (p < 0.0001). LAMR expression, which was positive in less than 50% of cells with weak staining, increased significantly between normal cervical epithelium and high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma, as well as between LSIL and HSIL (p < 0.0001). Between LSIL and invasive carcinoma, a significant increment was also observed for weak staining in less than 50% of cells (p < 0.001). LAMR expression, which was positive in more than 50% of cells with strong staining, was significantly higher in normal cervical tissue compared to the other groups (p < 0.0001). Disease progression related gradual increment of LAMR expression from normal cervical epithelium or LSIL towards HSIL or cervical cancer reveals that LAMR may play an important role in the transition from premalignant to malignant state in cervical lesions.

Channeling the Natural Properties of Sindbis Alphavirus for Targeted Tumor Therapy.

Sindbis alphavirus vectors offer a promising platform for cancer therapy, serving as valuable models for alphavirus-based treatment. This review emphasizes key studies that support the targeted delivery of Sindbis vectors to tumor cells, highlighting their effectiveness in expressing tumor-associated antigens and immunomodulating proteins. Among the various alphavirus vectors developed for cancer therapy, Sindbis-vector-based imaging studies have been particularly extensive. Imaging modalities that enable the in vivo localization of Sindbis vectors within lymph nodes and tumors are discussed. The correlation between laminin receptor expression, tumorigenesis, and Sindbis virus infection is examined. Additionally, we present alternative entry receptors for Sindbis and related alphaviruses, such as Semliki Forest virus and Venezuelan equine encephalitis virus. The review also discusses cancer treatments that are based on the alphavirus vector expression of anti-tumor agents, including tumor-associated antigens, cytokines, checkpoint inhibitors, and costimulatory immune molecules.

Laminin regulates oligodendrocyte development and myelination.

Oligodendrocytes are the cells that myelinate axons and provide trophic support to neurons in the CNS. Their dysfunction has been associated with a group of disorders known as demyelinating diseases, such as multiple sclerosis. Oligodendrocytes are derived from oligodendrocyte precursor cells, which differentiate into premyelinating oligodendrocytes and eventually mature oligodendrocytes. The development and function of oligodendrocytes are tightly regulated by a variety of molecules, including laminin, a major protein of the extracellular matrix. Accumulating evidence suggests that laminin actively regulates every aspect of oligodendrocyte biology, including survival, migration, proliferation, differentiation, and myelination. How can laminin exert such diverse functions in oligodendrocytes? It is speculated that the distinct laminin isoforms, laminin receptors, and/or key signaling molecules expressed in oligodendrocytes at different developmental stages are the reasons. Understanding molecular targets and signaling pathways unique to each aspect of oligodendrocyte biology will enable more accurate manipulation of oligodendrocyte development and function, which may have implications in the therapies of demyelinating diseases. Here in this review, we first introduce oligodendrocyte biology, followed by the expression of laminin and laminin receptors in oligodendrocytes and other CNS cells. Next, the functions of laminin in oligodendrocyte biology, including survival, migration, proliferation, differentiation, and myelination, are discussed in detail. Last, key questions and challenges in the field are discussed. By providing a comprehensive review on laminin's roles in OL lineage cells, we hope to stimulate novel hypotheses and encourage new research in the field.

Expression and significance of laminin receptor in squamous cell carcinoma of the tongue.

Laminin receptor is a non-integrin cell-surface receptor that binds laminin present on the basement membrane. It has been reported to be associated with infiltration and metastasis of various malignant tumors. However, no studies regarding tongue cancer have been reported. This study aimed to clarify the role of laminin receptor in squamous cell carcinoma of the tongue. We performed immunohistochemical staining of specimens from 66 patients with squamous cell carcinoma of the tongue and assessed laminin receptor expression and clinicopathological factors. As epithelial-mesenchymal transition has been shown to be associated with infiltration and metastasis of malignant tumors, staining for E-cadherin, vimentin, and N-cadherin were also performed. Of 20 patients with postoperative recurrence, 14 exhibited high laminin receptor expression (p = 0.0025). Kaplan-Meier analysis revealed a significantly shorter time to postoperative recurrence for the high laminin receptor expression group than that for the low laminin receptor expression group (p = 0.0008). Based on multivariate analyses for postoperative recurrence, high laminin receptor expression was associated with poor prognosis (high expression vs. low expression; HR =3.19, 95% CI =0.92-11.08; p = 0.0682). There was a correlation between laminin receptor and N-cadherin (p = 0.0089) but not between laminin receptor and E-cadherin (p = 0.369) or vimentin (p = 0.4221). These results suggest that high laminin receptor expression is a useful prognostic factor for postoperative recurrence and may be a target for molecular therapy to treat squamous cell carcinoma of the tongue.

Epigallocatechin-3-gallate stimulates StAR expression and progesterone production in human granulosa cells through the 67-kDa laminin receptor-mediated CREB signaling pathway.

Epigallocatechin-3-gallate (EGCG) is the most abundant and biologically active catechins extracted from green tea. The health benefits of EGCG have been extendedly studied. Ovarian steroidogenesis plays a pivotal role in maintaining normal reproductive function. Granulosa cells in the ovary are essential for steroid hormone production. To date, the effect of EGCG on steroidogenesis in human granulosa cells remains unclear. In the present study, we examine the physiological concentrations of EGCG on steroidogenesis in a steroidogenic human granulosa-like tumor cell line, KGN. Our results demonstrate that treatment with EGCG upregulates steroidogenic acute regulatory protein (StAR) expression and increases progesterone (P4) production. EGCG does not affect the expression levels of other steroidogenesis-related enzymes, such as P450 side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase, and aromatase. In addition, we identify the expression of 67-kDa laminin receptor (67LR) in KGN cells. Moreover, EGCG-induced StAR expression and P4 production require the 67LR-mediated activation of the PKA-CREB signaling pathway. These results provide a better understanding of the function of EGCG on ovarian steroidogenesis, which may lead to the development of alternative therapeutic approaches for reproductive disorders.

The Expression of PEDF and its Putative Receptors in Hepatocellular Carcinoma and Background Liver Tissue.

Hepatocellular carcinoma (HCC) remains one of the biggest medical issues. Pigment epithelial-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF interacts with its two receptors, adipose triglyceride lipase (ATGL) and laminin receptor (LR). We conducted immunohistochemical staining for PEDF, LR and ATGL in 151 resected HCCs and their background liver tissues. High expression of LR in HCC was associated with high histological grade and portal vein invasion, while high expression of PEDF in HCC was associated with absence of portal vein invasion. High LR expression in background liver was statistically associated with low serum albumin levels and was an independent prognostic factor of worse outcomes. No cases with more than 5% fatty degeneration in the background liver tissue showed high PEDF expression. PEDF/LR/ATGL could be potential biomarkers in HCC and various chronic hepatic disorders.

The Regional Specific Alterations in BBB Permeability are Relevant to the Differential Responses of 67-kDa LR Expression in Endothelial Cells and Astrocytes Following Status Epilepticus.

Status epilepticus (a prolonged seizure activity, SE) differently affects vasogenic edema formation and dystrophin-aquaporin 4 (AQP4) expressions between the rat hippocampus and the piriform cortex (PC). In the present study, we explored whether the 67-kDa laminin receptor (LR) expression was relevant to the regional specific susceptibility of vasogenic edema at 3 days after SE. In spite of no difference in expression levels of 67-kDa LR, dystrophin, and AQP4 under physiological conditions, SE-induced serum extravasation was more severe in the PC than the hippocampus. Western blots demonstrated that SE reduced expression levels of 67-kDa LR, dystrophin, and AQP4 in the PC, but not in the hippocampus proper. Immunofluorescent studies revealed that SE increased 67-kDa LR expression in reactive CA1 astrocyte, but reduced it in the PC and the molecular layer of the dentate gyrus due to massive astroglial loss. Furthermore, SE decreased expressions of endothelial 67-kDa LR and SMI-71 (endothelial brain barrier antigen) in these regions. The 67-kDa LR neutralization evoked serum extravasation in these regions of normal animals without astroglial loss. Similar to SE, 67-kDa LR neutralization also reduced dystrophin-AQP4 expressions in the PC more than the total hippocampus. Furthermore, 67-kDa LR IgG infusion increased phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), but not c-Jun N-terminal kinase, independent of phosphoprotein enriched in astrocytes of 15 kDa (PEA15) activity. Co-treatment of U0126 (an ERK1/2 inhibitor) alleviated vasogenic edema formation and the reduced dystrophin-AQP4 expressions induced by 67-kDa LR neutralization. The 67-kDa LR IgG infusion also increased the susceptibility to SE induction. Therefore, our findings suggested that the cellular specific alterations in 67-kDa LR expression might be involved in the severity of SE-induced vasogenic edema formation in regional specific manners, which might affect the susceptibility to SE induction.

Integrin α6 as an invasiveness marker for hepatitis B viral X-driven hepatocellular carcinoma.

Hepatitis B virus (HBV) accounts for more than 60% of hepatocellular carcinoma (HCC) cases. However, there is limited information about the features of HBV-driven HCC that differentiate it from other types of HCC. The aim of this study is to find a gene specific to HBV-driven HCC and understand its role during tumorigenesis. The differences in gene expression patterns were analyzed among patients with hepatitis virus-unrelated liver cirrhosis, and hepatitis C virus- and HBV-driven HCC. Genes expressed only in HBV patients were compared to genes of transgenic mice expressing hepatitis B viral X gene. Integrin α6 was commonly overexpressed in both HBV-driven HCC patients and transgenic mice expressing viral X. This gene's activation induced overexpression of integrin α6, as well as formation of integrins α6β1 and α6β4, without changing the expression of non-integrin laminin receptors. Suppression of integrin α6 caused significant inhibition of tumor migration in vitro. This study found a significant association between HBV and integrin α6, which may be responsible for early migration and invasion of HCC. Thus, integrin α6 is a predictive marker for tumor recurrence and invasiveness of HBV-driven HCC.

Pigment epithelium-derived factor promotes tumor metastasis through an interaction with laminin receptor in hepatocellular carcinomas

Pigment epithelium-derived factor (PEDF) has complex functions in tumor metastasis, but little is known about the roles of PEDF and its receptors in hepatocellular carcinoma (HCC). Here we found that high expression of PEDF is associated with shorter overall survival in HCC patients. Forced expression of PEDF enhanced HCC cell aggressive behavior in vitro and in vivo, whereas silencing PEDF expression reduced migration and invasion. Furthermore, PEDF expression led to changes in cell morphology and the expression of epithelial–mesenchymal transition (EMT)-related markers via ERK1/2 signaling pathway, including the upregulation of N-cadherin and slug, and the downregulation of E-cadherin in HCC cells. Our results further showed that PEDF could interact with laminin receptor (LR) and LR knockdown attenuated PEDF-induced migration, invasion and the change of EMT-related markers. More importantly, in clinical HCC specimens, we found that PEDF expression was correlated with subcellular localization of LR, and that high expression of PEDF and positive expression of LR predicted a poor prognosis. In conclusion, our results demonstrate a novel functional role of PEDF/LR axis in driving metastasis through ERK1/2-mediated EMT in HCC and provided a promising prognostic marker in HCC.

Effect of Perilla frutescens Extracts on Porcine Jejunal Epithelial Cells.

Green-leaved Perilla frutescens extracts were investigated on their effect on cell proliferation of the porcine jejunal epithelial cell line, IPEC-J2, as well as on the gene expression of cell cycle or cancer-related genes. Some extracted compounds were, however, susceptible to degradation in cell culture medium, whereas others were found to be stable during the entire experimental time. Control experiments also included the assessment of H2 O2 generation in cell culture medium caused by oxidation of natural extract compounds, which was proved to be absent at low extract concentrations. A fast and significant inhibition of cell growth at low physiological extract concentrations could be observed. This finding, along with an immediate downregulation of 67 kDa laminin receptor and cyclin D1 expression, can be accounted to the presence of Perilla frutescens extract. Copyright © 2016 John Wiley & Sons, Ltd.

YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells.

Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons, using known receptors, signals and transcription factors. In contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice we show that Taz is required in Schwann cells for radial sorting and myelination, and that Yap is redundant with Taz. Yap/Taz are activated in Schwann cells by mechanical stimuli, and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for proper radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.

Epigallocatechin-3-gallate Increases RXRγ-mediated Pro-apoptotic and Anti-invasive Effects in Gastrointestinal Cancer Cell Lines.

Molecules with synergistic effects often enhance the benefits of cancer therapy. We observed that the major catechin of green tea, (-)-Epigallocatechin-3-gallate (EGCG), induced retinoid X receptor-γ (RXRγ) expression in the SK-Ch-A1 cholangiocarcinoma cell line and in two colon carcinoma cell lines (LoVo and the derivative multi-drug resistant LoVoMDR). On this basis, we analyzed the effects of EGCG in combination with an RXRγ ligand, 6-OH-11-O-hydroxyphenantrene (IIF), or with a ligand of retinoic acid receptor, all-trans-retinoic acid (RA). IIF alone and in combination with EGCG activated the retinoic X response elements and induced the germ cell nuclear factor. In parallel, EGCG induced 67 kDa laminin receptor expression alone and in combination with IIF. We observed a synergistic growth inhibition with EGCG and IIF in combination at lower doses. These effects were accompanied by apoptosis activation through the mitochondrial pathway. Moreover, in LoVo cell line we observed an induction of Forkhead box O3 expression, another molecule involved in apoptosis activation. Finally, metalloproteinase activity and extracellular matrix metalloproteinase inducer (EMMPRIN) expression were inhibited and tumor cell invasion was strongly reduced in the SK-Ch-A1 cell line after treatment with EGCG and IIF. In conclusion, the use of specific RXR ligands in combination with catechins could open a new perspective in gastrointestinal tumor chemoprevention.

Mesoangioblast delivery of miniagrin ameliorates murine model of merosin-deficient congenital muscular dystrophy type 1A.

BackgroundMerosin-deficient congenital muscular dystrophy type-1A (MDC1A) is characterized by progressive muscular dystrophy and dysmyelinating neuropathy caused by mutations of the α2 chain of laminin-211, the predominant laminin isoform of muscles and nerves. MDC1A has no available treatment so far, although preclinical studies showed amelioration of the disease by the overexpression of miniagrin (MAG). MAG reconnects orphan laminin-211 receptors to other laminin isoforms available in the extracellular matrix of MDC1A mice.MethodsMesoangioblasts (MABs) are vessel-associated progenitors that can form the skeletal muscle and have been shown to restore defective protein levels and motor skills in animal models of muscular dystrophies. As gene therapy in humans still presents challenging technical issues and limitations, we engineered MABs to overexpress MAG to treat MDC1A mouse models, thus combining cell to gene therapy.ResultsMABs synthesize and secrete only negligible amount of laminin-211 either in vitro or in vivo. MABs engineered to deliver MAG and injected in muscles of MDC1A mice showed amelioration of muscle histology, increased expression of laminin receptors in muscle, and attenuated deterioration of motor performances. MABs did not enter the peripheral nerves, thus did not affect the associated peripheral neuropathy.ConclusionsOur study demonstrates the potential efficacy of combining cell with gene therapy to treat MDC1A.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-015-0055-5) contains supplementary material, which is available to authorized users.

Endocytic trafficking of laminin is controlled by dystroglycan and is disrupted in cancers.

The dynamic interactions between cells and basement membranes serve as essential regulators of tissue architecture and function in metazoans, and perturbation of these interactions contributes to the progression of a wide range of human diseases, including cancers. Here, we reveal the pathway and mechanism for the endocytic trafficking of a prominent basement membrane protein, laminin-111 (referred to here as laminin), and their disruption in disease. Live-cell imaging of epithelial cells revealed pronounced internalization of laminin into endocytic vesicles. Laminin internalization was receptor mediated and dynamin dependent, and laminin proceeded to the lysosome through the late endosome. Manipulation of laminin receptor expression revealed that the dominant regulator of laminin internalization is dystroglycan, a laminin receptor that is functionally perturbed in muscular dystrophies and in many cancers. Correspondingly, laminin internalization was found to be deficient in aggressive cancer cells displaying non-functional dystroglycan, and restoration of dystroglycan function strongly enhanced the endocytosis of laminin in both breast cancer and glioblastoma cells. These results establish previously unrecognized mechanisms for the modulation of cell-basement-membrane communication in normal cells and identify a profound disruption of endocytic laminin trafficking in aggressive cancer subtypes.

Human umbilical cord mesenchymal stromal cells exhibit immature nucleus pulposus cell phenotype in a laminin-rich pseudo-three-dimensional culture system

IntroductionCell supplementation to the herniated or degenerated intervertebral disc (IVD) is a potential strategy to promote tissue regeneration and slow disc pathology. Human umbilical cord mesenchymal stromal cells (HUCMSCs) – originating from the Wharton’s jelly – remain an attractive candidate for such endeavors with their ability to differentiate into multiple lineages. Previously, mesenchymal stem cells (MSCs) have been studied as a potential source for disc tissue regeneration. However, no studies have demonstrated that MSCs can regenerate matrix with unique characteristics matching that of immature nucleus pulposus (NP) tissues of the IVD. In our prior work, immature NP cells were found to express specific laminin isoforms and laminin-binding receptors that may serve as phenotypic markers for evaluating MSC differentiation to NP-like cells. The goal of this study is to evaluate these markers and matrix synthesis for HUCMSCs cultured in a laminin-rich pseudo-three-dimensional culture system.MethodsHUCMSCs were seeded on top of Transwell inserts pre-coated with Matrigel™, which contained mainly laminin-111. Cells were cultured under hypoxia environment with three differentiation conditions: NP differentiation media (containing 2.5% Matrigel™ solution to provide for a pseudo-three-dimensional laminin culture system) with no serum, or the same media supplemented with either insulin-like growth factor-1 (IGF-1) or transforming growth factor-β1 (TGF-β1). Cell clustering behavior, matrix production and the expression of NP-specific laminin and laminin-receptors were evaluated at days 1, 7, 13 and 21 of culture.ResultsData show that a pseudo-three-dimensional culture condition (laminin-1 rich) promoted HUCMSC differentiation under no serum conditions. Starting at day 1, HUCMSCs demonstrated a cell clustering morphology similar to that of immature NP cells in situ and that observed for primary immature NP cells within the similar laminin-rich culture system (prior study). Differentiated HUCMSCs under all conditions were found to contain glycosaminoglycan, expressed extracellular matrix proteins of collagen II and laminin α5, and laminin receptors (integrin α3 and β4 subunits). However, neither growth factor treatment generated distinct differences in NP-like phenotype for HUCMSC as compared with no-serum conditions.ConclusionsHUCMSCs have the potential to differentiate into cells sharing features with immature NP cells in a laminin-rich culture environment and may be useful for IVD cellular therapy.

Aberrant expression of GATA binding protein 6 correlates with poor prognosis and promotes metastasis in cholangiocarcinoma

AimGATA6, a zinc-finger transcription factor, functions as a tumour promoter or suppresser according to different tumour origins. We investigated the clinical significance of GATA6 and its role in invasion and metastasis in cholangiocarcinoma (CCA). MethodsExpression of GATA6 in 87 cancerous, 24 paracancerous, 32 lymph-node metastatic and 8 liver metastatic samples from 87 CCA patients undergoing surgical resection was detected by immunohistochemistry. Impact of GATA6 on invasion, metastasis and 67kDa laminin receptor expression (67LR) was evaluated in CCA cells by shRNA lentivirus or expressed-plasmid transfection. ResultsAberrant expression of GATA6 in CCAs was significantly associated with lymph-node metastasis. GATA6 expression was higher in lymph-node and liver metastatic tissues compared with primary cancerous tissues. Kaplan–Meier analysis showed GATA6 expression correlated with poor overall survival and early recurrence in CCAs. Cox analysis suggested GATA6 was an independent prognostic marker for overall survival and recurrence-free survival. CCA cell invasion and migration were decreased by GATA6 knockdown and enhanced by GATA6 overexpression in vitro. Knockdown of GATA6 reduced CCA cell metastasis by xenotransplantation into nude mice. 67LR, which is overexpressed in CCAs and promotes invasion and metastasis through several pathways, positively correlated with GATA6 expression in 87 CCAs. Both mRNA and protein levels of 67LR were regulated by GATA6 in CCA cells. Moreover, ChIP analysis showed GATA6 bound to 67LR gene promoter in CCA cells. ConclusionAberrant expression of GATA6 correlates with poor prognosis and promotes invasion and metastasis in CCA.

Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence

Rapamycin, a potent immunomodulatory drug, has shown promise in the amelioration of numerous age-associated diseases including cancer, Alzheimer's disease and cardiac hypertrophy. Yet the elderly, the population most likely to receive therapeutic rapamycin, are already at increased risk for infectious disease; thus concern exists that rapamycin may exacerbate age-associated immune dysfunctions and worsen infection outcomes. Herein, we examined the impact of enteric delivered rapamycin monotherapy (eRapa) on the susceptibility of aged (22–24month) C57BL/6 mice to Streptococcus pneumoniae, the leading bacterial cause of community-acquired pneumonia. Following challenge with S. pneumoniae, administration of eRapa conferred modest protection against mortality. Reduced mortality was the result of diminished lung damage rather than reduced bacterial burden. eRapa had no effect on basal levels of Interleukin (IL)-1α, IL-6, IL-10, IL-12p70, KC, Interferon-γ, Tumor necrosis factor α and Monocyte chemotactic protein-1 in whole lung homogenates or during pneumococcal pneumonia. Previously we have demonstrated that cellular senescence enhances permissiveness for bacterial pneumonia through increased expression of the bacterial ligands Laminin receptor (LR), Platelet-activating factor receptor (PAFr) and Cytokeratin 10 (K10). These proteins are co-opted by S. pneumoniae and other respiratory tract pathogens for host cell attachment during lung infection. UM-HET3 mice on eRapa had reduced lung cellular senescence as determined by levels of the senescence markers p21 and pRB, but not mH2A.1. Mice on eRapa also had marked reductions in PAFr, LR, and K10. We conclude that eRapa protected aged mice against pneumonia through reduced lung cellular senescence, which in turn, lowered bacterial ligand expression.

Hypoxia enhances colon cancer migration and invasion through promotion of epithelial-mesenchymal transition

BackgroundA hypoxic environment exists in most solid tumors because in rapidly growing tumors, the development of angiogenic vasculature is heterogenous, usually not enough to overcome the necessary oxygen supply. In an ischemic condition, cancer cells develop escape mechanisms to survive and leave the unfavorable environment. That result in the acquisition of increased potential for local invasion and evasion to distant organs. However, the escape mechanisms of cancer cells from hypoxic stress have not been fully characterized. Materials and methodsThe human colon cancer cell line LoVo was cultured in hypoxia, and the adhesive and migratory properties were analyzed. The expression of cell surface and cytoplasmic molecules was also investigated. ResultsUnder hypoxic conditions, cells developed epithelial-mesenchymal transition. The expression levels of α2, α5, and β1 integrins were significantly upregulated and, as a consequence, the ability to adhere to and migrate on collagen and fibronectin was increased. On the other hand, the expression of 67-kDa laminin receptor and the abilities to adhere to and migrate on laminin were decreased. Additionally, the expression of CXCR4 was significantly increased on cells cultured in hypoxia, and the chemotactic activity to stromal cell–derived factor 1α was remarkably increased. ConclusionsHypoxic stress induced active epithelial-mesenchymal transition in colon cancer cells, with the typical morphologic and functional changes. These morphologic and functional changes of β1 integrins, the 67-kDa laminin receptor, and CXCR4 may be essential for the acquisition of the invasive and metastatic features in colorectal cancer.

Tumor-specific targeting with modified Sindbis viral vectors: evaluation with optical imaging and positron emission tomography in vivo.

Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option. The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo. All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines. We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.

Oxygen partial pressure modulates 67-kDa laminin receptor expression, leading to altered activity of the green tea polyphenol, EGCG

(−)-Epigallocatechin-3-O-gallate (EGCG) exhibits anti-tumor activity mediated via the 67-kDa laminin receptor (67LR). In this study, we found that 67LR protein levels are reduced by exposure to low O2 levels (5%), without affecting the expression of HIF-1α. We also found that EGCG-induced anti-cancer activity is abrogated under low O2 levels (5%) in various cancer cells. Notably, treatment with the proteasome inhibitor, prevented down-regulation of 67LR and restored sensitivity to EGCG under 5% O2. In summary, 67LR expression is highly sensitive to O2 partial pressure, and the activity of EGCG can be regulated in cancer cells by O2 partial pressure.