Laminin Γ1 Research Articles

Anopheles gambiae laminin interacts with the P25 surface protein of Plasmodium berghei ookinetes

Laminin is a major constituent of the basal lamina surrounding the midgut of the malaria vectors that has been implicated in the development of the Plasmodium oocyst. In this report we describe the cloning of the Anopheles gambiae gene encoding the laminin γ1 polypeptide and follow its expression during mosquito development. To further investigate the putative role of laminin in the transmission of the malaria parasite we studied the potential binding of the P25 surface protein of Plasmodium berghei using a yeast two-hybrid system. Heterodimer formation was observed and does not require any additional protein factors since purified fusion proteins can also bind each other in vitro. Laminin γ1 also interacts with the paralogue of P25, namely P28, albeit more weakly, possibly explaining why the two parasite proteins can substitute for each other in deletion mutants. This represents the first direct evidence for molecular interactions between a surface protein of the Plasmodium parasite with an Anopheles protein; the strong interplay between laminin γ1 and P25 suggests that this pair of proteins may function as a receptor/ligand complex regulating parasite development in the mosquito vector.

Sole expression of laminin gamma 2 chain in invading tumor cells and its association with stromal fibrosis in lung adenocarcinomas.

Laminin‐5 (LN‐5), an important basement membrane (BM) protein consisting of laminin α3, β3 and γ2 chains, has been suggested to be involved in tumor cell invasion and tissue repair. In this study, the distribution of the LN‐5 subunits in atypical adenomatous hyperplasia (AAH)and different types of adenocarcinomas of the lung was examined by immunohistochemical analysis. In AAH and non‐sclerosing, well‐differentiated adenocarcinomas, the LN γ2 chain was frequently detected along with the continuous BMs. These BMs were also positive for both LNα3 and β3 chains, suggesting that LN‐5 had been deposited. In contrast, the cytoplasmic staining for the LNγ2 chain was frequently observed in tumor cells of sclerosing, well‐differentiated adenocarcinomas, as well as of moderately and poorly differentiated adenocarcinomas, without any evidence of co‐expression of the LNα3 and β3 chains. This staining pattern of the LNγ2 chain was prominent in carcinoma cells invading into interstitial stroma and was associated with the formation of a central scar in the tumor tissues. These results suggest that the LNγ2 chain monomer could be an important indicator of progression of lung adenocarcinoma.

Laminin-8 (α4β1γ1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation

Laminins are a growing family of large heterotrimeric proteins with cell adhesive and signalling functions. They are major components of basement membranes and are found in many organs, including the vasculature and other compartments of bone marrow, thymus, lymph nodes and spleen. However, expression, recognition and use of laminin isoforms by lymphoid cells are poorly understood. In the present study, lymphoid T cells (Jurkat) were found to synthesize laminin alpha4, beta1 and gamma1 mRNAs and polypeptides and to assemble the chains into laminin-8. Lymphoblastoid B (NAD-20) cells, lymphoid NK (NKL) cells and blood lymphocytes also contained laminin-8 and, after cell permeabilization, practically all blood lymphocytes reacted with mAbs to laminin beta1 and gamma1 chains. Following stimulation, blood lymphocytes secreted laminin-8, and this laminin isoform, but not laminin-10/11(alpha5beta1gamma1/alpha5beta2gamma1), promoted chemokine-induced migration of the cells. In an activation-dependent manner, purified blood CD4 T cells adhered to immobilized laminin-8 and laminin-10/11 by using alpha6beta1 integrin, but minimally to laminin-1 (alpha1beta1gamma1). Accordingly, laminin-8 and laminin-10/11, but not laminin-1, strongly costimulated proliferation of the T cells via the same integrin. Thus, lymphoid cells are able to synthesize and secrete complete laminin molecules. In addition, synthesis of laminin-8 and recognition of laminin-8 and -10/11 by lymphocytes indicate relevance of these laminin isoforms in lymphocyte physiology.

Structural Analysis and Mutation Detection Strategy for the Human LamC3 Gene

Laminins are heterotrimeric extracellular matrix molecules, present in a wide range of basement membranes within human tissues. They consist of a combination of different α, β, and γ subunits. Three different γ subunits have been described to date. Two of them, the γ1 and γ2 chains are constituents of basement membrane related laminins, while the γ3 chain was detected in skin, heart, lung, reproductive tract, brain, and in the retina. Unlike other laminins, the expression of the γ3 chain was localized to peripheral nerves and to the apical surface of ciliated epithelial cells and in the retina. To further investigate the function and the possible pathogenic role of laminin γ3 in human disease, we elucidated the structure of the corresponding LAMC3 gene which encodes this polypeptide. Here we report the genomic organization of the LAMC3 gene and a mutation detection strategy for use in genetic studies.

Colon Cancer Cells Adhesion and Spreading on Autocrine Laminin-10 Is Mediated by Multiple Integrin Receptors and Modulated by EGF Receptor Stimulation

Epidermal growth factor (EGF) receptor ligands such as EGF and transforming growth factor-α (TGF-α) play an important role in controlling the proliferation, survival, morphology, and motility of colonic epithelial cells. There is also increasing evidence that growth factors and extracellular matrix (ECM) proteins cooperate to regulate these cellular processes. We have reported previously that autocrine TGF-α and an unidentified ECM protein in the serum-free conditioned medium of the human colon carcinoma cell line LIM1215 synergize to induce spreading of these cells in low-density cultures. We have now purified the ECM protein secreted by LIM1215 cells and show that it synergizes with EGF to induce spreading of LIM1215 cells and other human cell lines from the colon and other tissues. The purified ECM migrated as a single protein band with an apparent molecular mass of approximately 800 kDa on SDS–PAGE under nonreducing conditions and, under reducing conditions, as three protein bands of approximately 360, 210, and 200 kDa. Immunoblotting experiments and mass spectrometry analysis of tryptic digests on the purified protein identified the 360-, 210-, and 200-kDa protein bands as laminin α5, β1, and γ1 chains, respectively, indicating that LIM1215 cells secrete laminin-10 (α5β1γ1). In serum-free medium, LIM1215 cells adhere to laminin-10 primarily via α2β1 and α3β1 integrin receptors. EGF-induced spreading of LIM1215 cells on laminin-10 is partially inhibited by pretreatment of the cells with blocking antibodies directed against integrin α3 or β1 but not α2, α6, or β4 subunits. Spreading is almost completely inhibited by blocking α3 + α2, α3 + α6, or β1 + β4 integrin chains and results in cell death. Increased spreading in the presence of EGF correlates with up-regulation of α6β4 integrins in these cells after exposure to EGF. These results indicate that colon cancer cells attach and spread on laminin-10 via multiple integrin receptors and suggest a critical role for α3β1 integrins in the spreading response. Together, our results support the concept that the adhesive properties of colon cancer cells are modulated by autocrine production of TGF-α and laminin-10 and autocrine induction of appropriate integrins.

Monocytic cells synthesize, adhere to, and migrate on laminin-8 (alpha 4 beta 1 gamma 1).

Laminins, a growing family of large heterotrimeric proteins with cell adhesive and signaling properties, are major components of vascular and other basement membranes. Expression, recognition, and use of laminin isoforms by leukocytes are poorly understood. In monoblastic THP-1 cells, transcripts for laminin gamma(1)-, beta(1)-, and alpha(4)-chains were detected by RT-PCR. Following immunoaffinity purification on a laminin beta(1) Ab-Sepharose column, laminin beta(1)- (220 kDa), gamma(1)- (200 kDa), and alpha(4)- (180/200 kDa) chains were detected by Western blotting in THP-1 cells and in two other monoblastic cell lines, U-937 and Mono Mac 6. After cell permeabilization, a mAb to laminin gamma(1)-chain reacted with practically all blood monocytes by immunofluorescence flow cytometry, and laminin-8 (alpha(4)beta(1)gamma(1)) could be isolated also from these cells. Monoblastic JOSK-I cells adhered constitutively to immobilized recombinant laminin-8, less than to laminin-10/11 (alpha(5)beta(1)gamma(1)/alpha(5)beta(2)gamma(1)) but to a higher level than to laminin-1 (alpha(1)beta(1)gamma(1)). Compared with the other laminin isoforms, adhesion to laminin-8 was preferentially mediated by alpha(6)beta(1) and beta(2) integrins. Laminin-8 and, to a lower extent, laminin-1 promoted spontaneous and chemokine-induced migration of blood monocytes, whereas laminin-10/11 was inhibitory. Altogether, the results indicate that leukocytes, as other cell types, are able to synthesize complete laminin molecules. Expression, recognition, and use of laminin-8 by leukocytes suggest a major role of this laminin isoform in leukocyte physiology.

Chain specificity assignment of monoclonal antibodies to human laminins by using recombinant laminin beta1 and gamma1 chains.

In the present study, the chain specificity of 16 commonly used monoclonal antibodies to human laminin(s) was analysed by using recombinant laminin beta1 and gamma1 chains. By ELISA, all antibodies reacted with purified placenta laminin, and most antibodies recognised either recombinant beta1 or gamma1 chains. Reactivity and chain specificity was confirmed against the recombinant chains in Western blotting under non-reducing conditions, and only a few antibodies were reactive under reducing conditions. Most antibodies were able to immunoprecipitate associated laminin beta1/gamma1 chains from platelet lysates. Based on these results and data from the literature, a tentative epitope map is presented.

Involvement of activator protein 1 complexes in the epithelium-specific activation of the laminin γ2-chain gene promoter by hepatocyte growth factor (scatter factor)

Laminin-5 is a trimer of laminin α3, β3 and γ2 chains that is found in the intestinal basement membrane. Deposition of the laminin γ2 chain at the basement membrane is of great interest because it undergoes a developmental shift in its cellular expression. Here we study the regulatory elements that control basal and cytokine-activated transcriptional expression of the LAMC2 gene, which encodes the laminin γ2 chain. By using transient transfection experiments we demonstrated the presence of constitutive and cytokine-responsive cis-elements. Comparison of the transcriptional activity of the LAMC2 promoter in the epithelial HT29mtx cells with that in small-intestinal fibroblastic cells (C20 cells) led us to conclude that two regions with constitutive epithelium-specific activity are present between positions -1.2 and -0.12 kb. This was further validated by transfections of primary foetal intestinal endoderm and mesenchyme. A 2.5 kb portion of the LAMC2 5ʹ flanking region was equally responsive to PMA and hepatocyte growth factor (HGF), whereas it was less responsive to transforming growth factor β1. A minimal promoter limited to the initial 120 bp upstream of the transcriptional start site maintained inducibility by PMA and HGF. This short promoter fragment contains two activator protein 1 (AP-1) elements and the 5ʹ-most of these is a composite AP-1/Sp1 element. The 5ʹAP-1 element is crucial to the HGF-mediated activity of the promoter; analysis of interacting nuclear proteins demonstrated that AP-1 proteins containing JunD mediate the response to HGF.

Differential expression of mouse laminin γ2 and γ2* chain transcripts

Differential expression of mouse laminin γ2 and γ2* chain transcripts

Differential expression of mouse laminin gamma2 and gamma2* chain transcripts.

Laminins are large heterotrimeric basement membrane proteins that consist of alpha, beta, and gamma chains. We have previously shown that the human gamma2 and gamma2* transcripts result from the alternative use of the LAMC2 gene 3'-end exons. To explore the biological significance of the alternative gamma2 transcripts, we isolated the cDNA coding for the mouse laminin gamma2* transcript, characterized the 3'-end of the murine LAMC2 gene, and studied the expression of alternative gamma2 transcripts in several mouse tissues. The sequence reported here is the first one containing a full-length gamma2* 3'-UTR from any species. The mouse gamma2* transcript is 4110 bases and encodes a putative polypeptide of 1110 amino acids. This polypeptide lacks the C-terminal cysteine residue thought to be important for heterotrimer formation. The mouse gamma2* transcript was found to be expressed in several tissues by polymerase chain reaction (PCR), but at very low levels. The clearest signals were obtained on embryonic day 7, and in heart and testis of adult tissues. When the laminin gamma2* transcript expression pattern was compared with that of the gamma2 chain, a similar tissue distribution was observed. There was, however, a significant difference in expression levels. The longer gamma2 transcript was found to be much more abundant than the shorter gamma2* variant. Moreover, by whole-mount in situ hybridization, the shorter gamma2* form was localized in the mesenchyme of the developing kidney whereas the longer gamma2 form was exclusively present in the epithelium of the Wolffian (nephric) duct and ureteric bud. The results indicate different functions for the gamma2 variants.

Erythromegakaryocytic Cells Synthesize Laminin-8 (α4β1γ1)

Blood platelets contain laminin-8 (α4β1γ1), a recently described laminin isoform, but the origin of platelet laminin is at present unknown. Laminin of platelets could be synthesized by megakaryocytes or, alternatively, endocytosed from plasma or other sources. In the present study, the synthesis and presence of laminin-8 in erythromegakaryocytic HEL and DAMI cells were explored. In HEL cells, transcripts for α4, β1, and γ1 laminin chains were readily detected by RT-PCR. Immunofluorescence flow cytometry demonstrated reactivity of mAbs to laminin β1 and γ1 chains with permeabilized cells. Metabolic labeling of HEL cells using [35S]methionine and [35S]cysteine followed by immunoprecipitation with monoclonal antibodies to β1 and γ1 chains revealed bands of approximately 220 and 200 kDa. In the HEL cell lysate, polypeptides of 220 and 200 kDa were recognized by monoclonal antibodies to laminin β1 and γ1 chains, respectively, whereas immunoaffinity-purified rabbit antibodies to laminin α4 chain gave inconclusive results. However, following immunoaffinity purification on a laminin β1 antibody–Sepharose column, a 200-kDa band was readily detected by the antibodies to laminin α4 chain. Similar results were obtained with DAMI cells. The size of laminin chains of HEL/DAMI cells was similar, though not identical, to the one of platelets, and the α4 chain was noncovalently associated to disulfide-bonded β1γ1 heterodimer, as in platelets. We conclude that erythromegakaryocytic cells synthesize laminin-8.

Blood Platelets Contain and Secrete Laminin-8 (α4β1γ1) and Adhere to Laminin-8 via α6β1 Integrin

Laminins, a family of heterotrimeric proteins with cell adhesive/signaling properties, are characteristic components of basement membranes of vasculature and tissues. In the present study, permeabilized platelets were found to react with a monoclonal antibody to laminin γ1 chain by immunofluorescence. In Western blot analysis of platelet lysates, several monoclonal antibodies to γ1 and β1 laminin chains recognized 220- to 230-kDa polypeptides, under reducing conditions, and a structure with much slower electrophoretic mobility under nonreducing conditions. Immunoaffinity purification on a laminin β1 antibody–Sepharose column yielded polypeptides of 230, 220, 200, and 180 kDa from platelet lysates. In the purified material, mAbs to β1 and γ1 reacted with the two larger polypeptides, while affinity-purified rabbit antibodies to laminin α4 chain recognized the smallest polypeptide. Identity of the polypeptides was confirmed by microsequencing. One million platelets contained on average 1 ng of laminin (approximately 700 molecules per cell), of which 20–35% was secreted within minutes after stimulation with either thrombin or phorbol ester. Platelets adhered to plastic surfaces coated with the purified platelet laminin, and this process was largely inhibited by antibodies to β1 and α6 integrin chains. We conclude that platelets contain and, following activation, secrete laminin-8 (α4β1γ1) and that the cells adhere to the protein by using α6β1 integrin.

Molecular Cloning and Tissue-specific Expression of a Novel Murine Laminin γ3 Chain

A novel laminin gamma3 chain was identified from the expressed sequence tag data base at the National Center for Biotechnology Information. A complete cDNAderived peptide sequence reveals a 1592-amino acid-long primary translation product, including a tentative 33-amino acid-long signal peptide. Comparison with the laminin gamma1 chain predicts that the two polypeptides have equal spatial dimensions. In addition, the well conserved domains VI and III(LE4) predict that gamma3 containing laminins are able to integrate to the laminin network and also via nidogen connect to other protein networks in the basement membranes. Combination of Northern analysis and in situ hybridization experiments indicate that expression of the gamma3 chain is highly tissue- and cell-specific, being significantly strong in capillaries and arterioles of kidney as well as in interstitial Leydig cells of testis.

Identification of endothelial cell binding sites on the laminin gamma 1 chain.

The laminins belong to a family of trimeric basement membrane glycoproteins with multiple domains, structures, and functions. Endothelial cells bind laminin-1 and form capillary-like structures when plated on a laminin-1-rich basement membrane matrix, Matrigel. Laminin-1 is composed of 3 chains, alpha1, beta1, and gamma1. Because laminin-1 is known to contain multiple biologically active sites, we have screened 156 synthetic overlapping peptides spanning the entire laminin gamma1 chain for potential angiogenic sequences. Only 7 of these peptides, designated as C16, C25, C30, C38, C64, C75, and C102, disrupted the formation of capillary-like structures by human umbilical vein endothelial cells on Matrigel. Dose-response experiments in the presence of 50 to 200 microg/mL showed that tube formation was prevented by most peptides at 150 and 200 microg/mL, except for C16, which showed strong activity at all concentrations. Active peptides promoted vessel sprouting from aorta rings and angiogenesis in the chick chorioallantoic membrane assay. In addition, the active peptides also promoted endothelial cell adhesion to dishes coated with 0.1 microg of peptide and inhibited attachment to laminin-1 but not to plastic or fibronectin. Four of the active peptides, C25, C38, C75, and C102, may have cell-type specificity with endothelial cells, since they did not promote PC12 neurite outgrowth or adhesion of B16-F10 melanoma and human submandibular gland cells. These results suggest that specific laminin gamma1-chain peptides have angiogenic activity with potential therapeutic applications.

Laminin 2 (merosin), but not laminin 1 (EHS-laminin), may be a major laminin isoform present in normal and fibrotic rat liver

Recently several laminin isoforms were newly identified and found to distribute in a tissue and cell type-specific manner. We have studied the expression of several laminin isoforms, including α1(A), α2(M), β1(B1), β2(S), and γ1(B2) subunits, in normal and CCl 4-induced fibrotic rat liver by RT-PCR and performed immunohistochemical study with newly developed monoclonal antibody to merosin (laminin-2). RT-PCR study for laminin subunits revealed that α2(M) subunit mRNA transcript was dominant chain present in normal rat liver tissue, but α1(A) subunit mRNA was not. Laminin β1(B1) and γ1(B2) subunit mRNA were detected strongly and β2(S) subunit mRNA was detected weakly. During the CCl 4-induced rat hepatic fibrosis, α2, β1, β2, and γ1 subunit mRNA showed increased expression, but α1 transcript could not be detected during fibrotic process even in the condition where α1 subunit mRNA was detectable in rat placental tissue. Immunohistochemical studies with a novel monoclonal antibody to merosin also revealed that deposition of merosin increased during CCl 4-induced rat fibrotic liver. These data strongly suggest that laminin isoform containing α2 subunit (merosin) may be a major laminin present in normal and fibrotic rat liver.

Absence of the laminin γ1 subunit causes early embryonic lethality by inhibition of basement membrane formation

Absence of the laminin γ1 subunit causes early embryonic lethality by inhibition of basement membrane formation

Nidogen-2: a new basement membrane protein with diverse binding properties

Human nidogen-2 was cloned and sequenced (1375 residues) and found to share 46% sequence identity and a similar domain arrangement with the previously characterized basement membrane protein nidogen-1. Recombinant nidogen-2 was purified as a 200 kDa protein from transfected mammalian cell medium, showed a high level of N and O-glycosylation, and could be clearly distinguished from nidogen-1 (150 kDa) by specific antibodies. Electron microscopy demonstrated that the two isoforms have a similar shape, consisting of three globular domains connected by two threads, but differ somewhat in length. Northern blots and immunological assays demonstrated co-expression of the nidogens in various tissues and cultured cells. Immunofluoresence revealed colocalization in vessel walls and other basement membrane zones but some differences in heart and skeletal muscle. Nidogen-2 interacted with collagens I and IV, and perlecan at a comparable level to nidogen-1 but failed to bind to fibulins. Nidogen-2 bound to laminin-1, but only moderately to the epitope on the laminin γ1 chain, which promotes high-affinity binding of nidogen-1. Both nidogens were cell-adhesive for a restricted number of cell lines, with nidogen-2 having a higher activity. Together, these data suggest that nidogen-2 can compensate for some but not all functional activities ascribed to nidogen-1.

Laminin gamma2 expression is developmentally regulated during murine tooth morphogenesis and is intense in ameloblasts.

Mutations in the laminin gamma2 gene cause junctional epidermolysis bullosa, and enamel hypoplasias are frequently seen in these patients. Laminin gamma2 is one of the three polypeptide chains forming the basement membrane glycoprotein laminin-5. We have localized the expression of the laminin gamma2 gene by in situ hybridization during mouse tooth development from early morphogenesis to completion of crown development. The expression was restricted to epithelial cells. During the early morphogenesis of the tooth germ, laminin gamma2 was expressed by the outer dental epithelium and by the stellate reticulum cells. No expression was detected in the cells of the inner dental epithelium giving rise to ameloblasts. The pre-ameloblasts remained negative during the early bell stage, but, interestingly, expression was very prominently upregulated as the cells differentiated into ameloblasts. This upregulation appeared to coincide with the start of enamel matrix secretion. The ameloblasts expressed laminin gamma2 intensely throughout the period of active enamel deposition. The expression continued at a lower level in the maturation-stage ameloblasts covering the enamel surface. Immunolocalization of laminin-5 with polyclonal antibodies indicated that the protein formed a continuous lining at the basal surfaces of the cells expressing the laminin gamma2 transcripts. We suggest that the role of laminin-5 during enamel formation may be to strengthen the anchorage of the ameloblasts to the enamel matrix, and that the pathogenesis of enamel hypoplasias in cases of laminin-5 mutations could be associated with detachment of the ameloblast cell layer from the enamel surface.

Wide Distribution of Laminin-5 γ2 Chain in Basement Membranes of Various Human Tissues

Laminin 5 (LN5), a heterotrimer of laminin α3, β3, and γ2 chains, is a laminin isoform which strongly promotes adhesion, migration, and scattering of cells through binding to integrins α3β1, α6β1 and α6β4. To get an insight into the physiological functions of LN5, we prepared a mouse monoclonal antibody to human laminin γ2 chain and used it for immunohistochemical analysis of laminin γ2 chain in normal human tissues. The basement membranes of various epithelial tissues, such as the skin, lung, small intestine, stomach, kidney and prostate, were immunostained with the anti-laminin γ2 chain monoclonal antibody. In addition, the basement membrane of the surface germinal epithelium in the ovary was also positive for laminin γ2 chain. These results suggest general roles of LN5 in the anchorage of various types of epithelial cells to the underlying basement membrane and in the expression of their cellular functions. Moreover, deposition of laminin γ2 chain around small arteries and veins was observed in the thymus and spleen. This lymphatic organ-specific expression of vascular LN5 might provide a novel function of LN5 in immune responses.

Laminin isoforms in non-tumoral and tumoral human livers: Expression of α1, α2, β1, β2 and γ1 chain mRNA and an α chain homologous to the α2 chain

Background/Aims: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells. Methods: Laminin α1, α2, β1, β2 and γ1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease ( n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas ( n=13) or metastases ( n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures. Results: Laminin α1, α2 and β1 mRNA were found in 25–33% and γ1 mRNA in 58% of the livers, the signal for laminin β2 mRNA being faint in all the samples. Laminin α2, β1, β2 and γ1 mRNA were expressed in hepatoma and stellate cells. The laminin α2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the α2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both α1 and α2 chains recognized polypeptides corresponding to the degradation products of α2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130 000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA. Conclusions: This first report on laminin isoforms in human livers indicates that laminin 1 (α1-β1-γ1), 2 (α2-β1-γ1), 3 (α1-β2-γ1) and 4 (α2-β2-γ1) mRNA and a polypeptide homologous to the α2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers.