Development Of Epithelial Tumors Research Articles

Comparative Study of Epithelial Tumor Development in General Hospitals in Iraq

Comparative Study of Epithelial Tumor Development in General Hospitals in Iraq

Transgenic overexpression of the miR-200b/200a/429 cluster prevents mammary tumor initiation in Neu/Erbb2 transgenic mice.

Although significant progress in the treatment of breast cancer has been achieved, toxic therapies would not be required if breast cancer could be prevented from developing in the first place. While breast cancer prevention is difficult to study in humans due to long disease latency and stochastic cancer development, transgenic mouse models with 100% incidence and defined mammary tumor onset, provide excellent models for tumor prevention studies. In this study, we used Neu/Erbb2 transgenic mice (MTB-TAN) as a model of human HER2+ breast cancer to investigate whether a family of microRNAs, known as the miR-200 family, can prevent mammary tumor development. Overexpression of Neu induced palpable mammary tumors in 100% of the mice within 38 days of Neu overexpression. When the miR-200b/200a/429 cluster was co-overexpressed with Neu in the same mammary epithelial cells (MTB-TANba429 mice), the miR-200b/200a/429 cluster prevented Neu from inducing mammary epithelial hyperplasia and mammary tumor development. RNA sequencing revealed alterations in the extracellular matrix of the mammary gland and a decrease in stromal cells including myoepithelial cells in Neu transgenic mice. Immunohistochemistry for smooth muscle actin confirmed that mammary epithelial cells in control and MTB-TANba429 mice were surrounded by a layer of myoepithelial cells and these myoepithelial cells were lost in MTB-TAN mice with hyperplasia. Thus, we have shown for the first time that elevated expression of miR-200 family members in mammary epithelial cells can completely prevent mammary tumor development in Neu transgenic mice possibly through regulating myoepithelial cells.

High Expression of Cancer-Derived Sialylated Immunoglobulin G: A Novel Biomarker for Poor Prognosis in Laryngeal Squamous Cell Carcinoma

Plain Language SummaryWhile cancer-derived sialylated immunoglobulin G (SIA-IgG) has been found to promote the development of various epithelial tumors, research on its role in laryngeal cancer remains blank. Therefore, the objective of this study is to investigate the correlation between LSCC expression and clinical prognosis as well as the proliferation and migration abilities of laryngeal cancer cells.

The mechanism of rapid development of epithelial tumors using the example of colorectal cancer

The mechanism of rapid development of epithelial tumors using the example of colorectal cancer

Incidence and the risk of occurrence of benign and malignant canine skin tumours in Poland - a five-year retrospective study.

The aim of the study was to compile data on the frequency and distribution of canine skin tumours and determine the risk of these being malignant as opposed to benign. This determination proceeded from tumour histogenesis and gave consideration to the dog's breed, sex, age and the anatomical location of tumours. This retrospective five-year epidemiological study included 3,139 canine skin tumours collected in Poland. A univariable logistic regression analysis was performed to determine the odds ratios (ORs) with 95% confidence intervals (CIs). Microscopic analysis showed a significant predominance of benign tumours (65.02%) as well as mesenchymal and melanocytic tumours (59.57%). The most frequently diagnosed were mast cell tumours, accounting for 13.79% of all skin tumours, and other common tumour types were lipomas (6.40%), haemangiopericytomas (5.96%) and malignant melanomas (4.65%). The risk of malignant versus benign tumours was 1.212 times higher in the female than in the male dogs. A higher risk of development of malignant epithelial tumours was found in boxers (OR 4.091), German shepherds (OR 4.085) and flat-coated retrievers (OR 43.596). A higher risk of development of malignant mesenchymal tumours was found in golden retrievers (OR 4.693), boxers (OR 2.342), bulldogs (OR 3.469) and Maltese (OR 2.757). The results may serve as a reference point for further studies of the complex biology of canine skin tumours.

Deciphering Stromal Changes between Metastatic and Non-metastatic Canine Mammary Carcinomas

Cancer-associated stroma (CAS) is widely recognized to influence development and progression of epithelial tumours including breast cancer. Canine mammary tumours (CMTs) such as simple canine mammary carcinomas represent valuable models for human breast cancer also with respect to stromal reprogramming. However, it remains unclear whether and how CAS changes in metastatic tumours compared to non-metastatic ones. To characterize stromal changes between metastatic and non-metastatic CMTs and identify potential drivers of tumour progression, we analysed CAS and matched normal stroma from 16 non-metastatic and 15 metastatic CMTs by RNA-sequencing of microdissected FFPE tissue. We identified 1438 differentially regulated genes between CAS and normal stroma, supporting previous results demonstrating stromal reprogramming in CMTs to be comparable with CAS in human breast cancer and validating deregulation of pathways and genes associated with CAS. Using primary human fibroblasts activated by treatment with TGFβ, we demonstrate some of the strongest expression changes to be conserved in fibroblasts across species. Furthermore, we identify 132 differentially expressed genes between CAS from metastatic and non-metastatic tumours, with strong changes in pathways including chemotaxis, regulation of apoptosis, immune response and TGFβ signalling and validate deregulation of several targets using RT-qPCR. Finally, we identify specific upregulation of COL6A5, F5, GALNT3, CIT and MMP11 in metastatic CAS, suggesting high stromal expression of these targets to be linked to malignancy and metastasis of CMTs. In summary, our data present a resource supporting further research into stromal changes of the mammary gland in relation to metastasis with implications for both canine and human mammary cancer.

O-152 Benign epithelial ovarian tumors following use of fertility drugs: a register-based cohort study from Denmark

Abstract Study question Is use of fertility drugs associated with an increased risk of benign epithelial ovarian tumors among women with infertility? Summary answer Among women with infertility, use of fertility drugs is not associated with an increased risk of benign epithelial ovarian tumors. What is known already Benign epithelial ovarian tumors are the most common neoplasms in the ovaries. These benign tumors share some of the same risk factors, which are associated with ovarian cancer. The general understanding of the pathogenesis and etiology of ovarian cancer is sparse; therefore, knowledge on factors influencing development of benign epithelial ovarian tumors—and hence likely ovarian cancer—is warranted. Previous studies on the association between fertility treatment and ovarian cancer are conflicting, whereas no previous study has examined the association between use of fertility drugs and benign epithelial ovarian tumors. Study design, size, duration Retrospective register-based cohort study of nearly 145,000 women included in the Danish Infertility Cohort during 1995–2017 at age 20–45 years. Women were followed from one year after infertility diagnosis until first benign epithelial ovarian tumor or one of the censoring criteria: borderline ovarian tumor, ovarian cancer, oophorectomy, emigration, death or end of follow-up (December 31, 2018). Participants/materials, setting, methods Using the Aalen-Johansen estimator, we determined 10-year cumulative risks of benign epithelial ovarian tumors among approximately 25,000 women who used fertility drugs (defined within one year after infertility diagnosis: clomiphene citrate, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone [GnRH] receptor modulators, and progesterone) compared with women diagnosed with infertility and no drug use. Additionally, we used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Main results and the role of chance Our results showed that the crude 10-year cumulative risk of benign epithelial ovarian tumors were 0.32% (95% CI: 0.29%–0.36%) for women who used any fertility drug compared with 0.49% (95% CI: 0.40%–0.60%) in women with no use of fertility drugs (risk difference: -0.17% [95% CI: -0.28–(-0.07)]). When adjusted for age, calendar period of infertility diagnosis, educational level, parity, obesity, polycystic ovary syndrome, and origin of infertility information, the HR for use of any fertility drug was 0.73 (95% CI 0.55–0.96). In general, the 10-year risk differences as well as the HRs for each drug evaluated separately were similar to the results for use of any drug. Lastly, we tested the robustness of our results by various pre-defined secondary analyses, and this did not change our results. Limitations, reasons for caution We did not include information on number of cycles and treatment regimens as these are only partly available in the registers. Wider implications of the findings Among women with infertility, we observe a lower relative risk of benign epithelial ovarian tumors for women treated with fertility drugs compared with women who did not use fertility drugs. However, this finding translates into a small decrease in absolute risk, which does not appear to have any clinical relevance. Trial registration number Not applicable

Expression of Salivary Immediate Early Response Gene X-1 as a Predictor of Malignancy in Epithelial Ovarian Tumor

Objective: This diagnostic study aims to determine the expression of salivary IEX-1 as a predictor of malignancy in epithelial ovarian tumors. 
 Methods: Samples were obtained from ovarian cancer patients who were scheduled for elective surgery. Patients' saliva was collected before surgery and used as the study's research material. Research subjects who met the inclusion and exclusion criteria were divided into two groups based on the post-operative histopathological results, benign and malignant epithelial ovarian tumors. The salivary IEX-1 expression was examined using the Real Time qPCR method. We compared and analyzed the salivary IEX-1 expression ​​in benign and malignant epithelial ovarian tumors. 
 Results: The results of this study were obtained from 47 epithelial ovarian tumors subjects, 22 malignant tumors and 27 benign tumors. The mean salivary IEX-1 expression in benign epithelial ovarian tumors was higher (1.976) than the malignant tumors (0.554) (p<0.001). The AUC value of IEX-1 expression was 0.949 (95% CI 0.894-1,000), cut off point of salivary IEX-1 is ≥ 0,9115 with sensitivity 84%, specificity 86,4%, positive predictive value 82.6% and negative predictive value 87.5%. There was a significant correlation between salivary IEX-1 expression and malignant epithelial ovarian tumors with an OR 5.031 (95% CI 2.039-12.4; p<0,001)
 Conclusion: Salivary IEX-1 expression declines in tandem with the development of malignant epithelial ovarian tumors, providing a very sensitive and specific indicator of the presence of these malignant tumors.
 Keywords: Expression of IEX-1, Malignant epithelial ovarian tumor, Salivary IEX-1, Tumor Marker.

DMARD treatment and skin cancer : Recognition, state of knowledge and prevention

Epithelial tumors differ in cellular origin, risk factors, incidence, and treatment. This article discusses the extent to which the use of disease-modifying antirheumatic drugs (DMARD) is associated with an increased risk for the development of skin tumors and for which substances the risk may be increased. In addition, some practical dermatological recommendations for rheumatologists are presented. The most frequent tumors of the skin are classified according to their cellular origin into malignant melanoma (MM) and so-called keratinocyte cancer (KC). The clinical presentation of these tumors differs and also the risk for the development of these epithelial skin tumors under DMARD treatment varies depending on the drug and tumor entity. As rheumatologists frequently see these patients for follow-up, it is essential to know the clinical findings as well as the corresponding risk factors of the specific tumor entities. Agenerally valid and reliable estimation of the risk for the development of epithelial skin tumors under DMARD treatment can only be formulated in the form of tendencies at the present time due to the lack of data. The relevant literature shows that regular intensive dermatological screening is recommended. Patients undergoing immunosuppressive or immune-modulating treatment should be instructed in self-inspection of the skin, receive regular dermatological check-ups and be instructed in strict UV protection methods. Lesions that do not heal or recurrently bleed should be referred for apunch biopsy to rule out or diagnose an epithelial skin tumor, as should atypical inflammatory lesions that do not heal with the use of topical glucocorticoids. An interdisciplinary approach in patient management is the key to success in ensuring the maximum quality of life with the lowest possible risk of developing epithelial skin tumors for these patients.

NEW DATA ON HISTOGENESIS AND HISTOLOGICAL STRUCTURE OF LUNG CANCER.

Lung cancer (LC) is one of the most common malignant neoplasms in men around the world, which poses a number of important challenges for scientists. To analyze the histogenesis, features of the histological structure, and growth of LC. The surgical material of 81 patients with LC was studied. Histological preparations were stained with hematoxylin and eosin (H&E) using the Papanicolaou method. Immunohistochemical reactions with monoclonals (Ki67, PCNA) were conducted. In histological preparations of all LC types (squamous, adenocarcinoma, and small cell), along with solid growth, tumor growth in the alveoli was determined, which started from the basal membrane and grew toward the alveolus center, as evidenced by the morphological features of growth, tumor spread, and development of necrosis in the center. In all the studied histological preparations of LC, tumor growth in the alveoli is noted, which is confirmed by structural and cellular signs and the nature of tumor decay in the alveolus center, which corresponds to the general patterns of development of malignant epithelial tumors.

Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis

The androgen receptor (AR)-signaling pathways are essential for prostate tumorigenesis. Although significant effort has been devoted to directly targeting AR-expressing tumor cells, these therapies failed in most prostate cancer patients. Here, we demonstrate that loss of AR in stromal sonic-hedgehog Gli1-lineage cells diminishes prostate epithelial oncogenesis and tumor development using in vivo assays and mouse models. Single-cell RNA sequencing and other analyses identified a robust increase of insulin-like growth factor (IGF) binding protein 3 expression in AR-deficient stroma through attenuation of AR suppression on Sp1-regulated transcription, which further inhibits IGF1-induced Wnt/β-catenin activation in adjacent basal epithelial cells and represses their oncogenic growth and tumor development. Epithelial organoids from stromal AR-deficient mice can regain IGF1-induced oncogenic growth. Loss of human prostate tumor basal cell signatures reveals in basal cells of stromal AR-deficient mice. These data demonstrate a distinct mechanism for prostate tumorigenesis and implicate co-targeting stromal and epithelial AR-signaling for prostate cancer.

088 Deciphering the molecular signals of EGFR pathway activation in Dlx3 deficient skin in cSCC

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. Emerging evidence suggests that homeoproteins can act as modulators of tumor initiation and progression in cSCC. DLX3 is a homeobox transcription factor which plays pivotal roles in embryonic development and epidermal homeostasis. Previous work from our lab, using both human samples and a Dlx3 knock-out (Dlx3cKO) mouse model, demonstrated DLX3’s tumor suppressive role in epithelial tumor development and tumor progression.

Ovarian tumors and genetic predisposition.

Summary of knowledge in the field of ovarian cancer and genetic predisposition. Ovarian tumors are usually diagnosed at advanced stages of the disease and the prognosis for these patients is generally poor. The 5-year overall survival rate, regardless of the histopathological type of tumor, is around 44%. Germline mutations causing hereditary tumor syndromes are predominantly involved in the development of epithelial ovarian tumors. The most common is hereditary breast and ovarian cancer syndrome, which is caused by germline mutations in the tumor suppressor genes BRCA1 and BRCA2. Several other tumor suppressor genes and oncogenes are known to be associated with ovarian tumors and cause other types of tumor syndromes. Inherited tumor syndromes include Lynch syndrome, Peutz-Jegers syndrome, Gorlin syndrome, Li-Fraumeni syndrome and others. The indication for genetic examination of germline mutations is given by a clinical geneticist on the basis of the recommendation of the attending physician. At present, every ovarian tumor, primary peritoneal tumor and tube tumor diagnosed at any age is indicated for genetic testing. Early identification of genes for hereditary cancer syndromes, thanks to rapidly developing molecular genetic methods, is an important step towards personalized treatment of ovarian cancer and preventive measures in families at risk. It is also important to note that a negative molecular genetic test result does not exclude genetic risk.

Экспрессия цитокератинов реактивно измененного цилиндрического реснитчатого эпителия синоназального тракта при хронических воспалительных процессах

Introduction. Currently, there are limited papers on changes in the pseudostratified ciliated columnar epithelium of the sinonasal tract in chronic inflammatory processes, particularly in basal cell hyperplasia. The latter is similar to dysplasia of varying severity of the stratified squamous nonkeratinized epithelium. Studying of changes in the pseudostratified ciliated columnar epithelium can clarify the histogenesis of various epithelial tumors of the sinonasal tract, including sinonasal papillomas. The research is aimed at studying the cytokeratin profile of reactive cylindrical ciliated epithelium in a chronic nonspecific inflammatory process. Materials and methods. We analyzed surgical materials obtained from 567 patients diagnosed with chronic rhinosinusitis with nasal polyps. We performed an immunohistochemical study in 20 cases using the panel of antibodies to Ki-67, Stathmin, Cytokeratin 7, Cytokeratin 10/13, Cytokeratin 14, Cytokeratin 17, Cytokeratin 18, and Cytokeratin 19. Results. Using hematoxylin and eosin staining, we detected basal cell hyperplasia of different severity in 74% (419 cases). In 13% (73 cases), basal cell hyperplasia was combined with foci of squamous metaplasia. Based on the results, we identified 4 types of morphological changes in the epithelial layer with a specific cytokeratin profile: mild basal cell hyperplasia, moderate basal cell hyperplasia, severe basal cell hyperplasia, and areas of squamous metaplasia. Conclusion. Simultaneous expression of cytokeratins in the areas with severe hyperplasia of basal cells, specific for both simple and compound epithelia, allows us to consider this area to have the highest potential for the development of various epithelial tumors of the sinonasal tract, including various types of sinonasal papillomas. Keywords: basal cell hyperplasia, sinonasal papilloma, pseudostratified columnar ciliated epithelium

Papillomavirus-associated neoplasms of dogs and cats

Papillomavirus oncogenesis as a benign process, clinically diagnosed as papillomatosis, is common in small domestic animals, in particular among cats and dogs, but in the nosological structure of neoplasms has a different ratio depending on the species. Recent data indicate the provocation of precancerous and neoplastic lesions in domestic species by the papillomatosis virus. Clinically, oncogenesis is associated with lesions of the skin and mucous membranes, which is determined by the tropicity of the virus, since the papillomavirus replication cycle is closely related to the differentiation of cells of the multilayer squamous epithelium, and in accordance with the morphological classification provokes the development of epithelial tumors without specific localization. The following neoplasms were identified in the structure of tumors of epithelial origin in dogs and cats: papilloma, squamous cell carcinoma and basal cell carcinoma. In statistical studies during the study period, organ-specific tumors in dogs amounted to 23.85%, in cats 12.5%. The concept of infectious oncology is used, which includes and combines the basic principles of infectious and oncological processes. Bibliographic analysis revealed the associativity of papillomavirus infection with specific neoplasms, depending on the taxonomy of the virus and the type of animal.

Ассоциированные с папилломавирусом новообразования собак и кошек

Papillomavirus oncogenesis as a benign process, clinically diagnosed as papillomatosis, is common in small domestic animals, in particular among cats and dogs, but in the nosological structure of neoplasms has a different ratio depending on the species. Recent data indicate the provocation of precancerous and neoplastic lesions in domestic species by the papillomatosis virus. Clinically, oncogenesis is associated with lesions of the skin and mucous membranes, which is determined by the tropicity of the virus, since the papillomavirus replication cycle is closely related to the differentiation of cells of the multilayer squamous epithelium, and in accordance with the morphological classification provokes the development of epithelial tumors without specific localization. The following neoplasms were identified in the structure of tumors of epithelial origin in dogs and cats: papilloma, squamous cell carcinoma and basal cell carcinoma. Histological diagnosis was carried out using the allocation of specific criteria characteristic of tumors, regardless of cytogenesis. In statistical studies during the study period, organ-specific tumors in dogs amounted to 23,85%, in cats 12,5%. It is noted that papillomavirus infection is characterized by the specificity of lesions not only within one species, many histological criteria for certain types of tumors are similar in both cats and dogs. The concept of infectious oncology is used, which includes and combines the basic principles of infectious and oncological processes. Bibliographic analysis revealed the associativity of papillomavirus infection with specific neoplasms, depending on the taxonomy of the virus and the type of animal.

Biological Defenses and Regulation of Epithelial Tumor Development by the Gastric Gland Mucus-type Glycan

Biological Defenses and Regulation of Epithelial Tumor Development by the Gastric Gland Mucus-type Glycan

The Merkel Cell Polyomavirus T Antigens Function as Tumor Promoters in Murine Skin.

Simple SummaryMerkel cell polyomavirus, a recently discovered human virus, is linked to the development of a rare form of skin cancer called Merkel cell carcinoma. The virus does not replicate in cancer cells, yet there is continued expression of viral proteins known as T antigens. The T antigens are believed to contribute to Merkel cell carcinoma development, yet how they do so remains an active area of research. In this study, we used transgenic mice expressing the viral T antigens in their skin to determine at which stage of skin cancer development these viral proteins function. We discovered that the Merkel cell polyomavirus T antigens function as tumor promoters, rather than tumor initiators, in the skin. These findings suggest that other tumor-initiating events may cooperate with the tumor-promoting activities of the viral T antigens, thus providing important insight into how Merkel cell polyomavirus can cause cancer in human skin.Merkel cell polyomavirus (MCPyV) causes the majority of human Merkel cell carcinomas (MCC), a rare but highly aggressive form of skin cancer. We recently reported that constitutive expression of MCC tumor-derived MCPyV tumor (T) antigens in the skin of transgenic mice leads to hyperplasia, increased proliferation, and spontaneous epithelial tumor development. We sought to evaluate how the MCPyV T antigens contribute to tumor formation in vivo using a classical, multi-stage model for squamous cell carcinoma development. In this model, two chemical carcinogens, DMBA and TPA, contribute to two distinct phases of carcinogenesis—initiation and promotion, respectively—that are required for tumors to develop. By treating the MCPyV transgenic mice with each chemical carcinogen, we determined how the viral oncogenes contributed to carcinogenesis. We observed that the MCPyV T antigens synergized with the tumor initiator DMBA, but not with the tumor promoter TPA, cause tumors. Therefore, the MCPyV tumor antigens function primarily as tumor promoters, similar to that seen with human papillomavirus (HPV) oncoproteins. These studies provide insight into the role of MCPyV T antigen expression in tumor formation in vivo and contribute to our understanding of how MCPyV may function as a human DNA tumor virus.

Elastin is a key factor of tumor development in colorectal cancer

BackgroundColorectal cancer (CRC) is the most common cancer and a leading cause of death worldwide. Extracellular matrix (ECM) proteins regulate tumor growth and development in CRC. Elastin (ELN) is a component of ECM proteins involved in the tumor microenvironment. However, the role of ELN in CRC remains unclear.MethodsIn this study, we analyzed ELN gene expression in tumors from CRC patients and adjacent non-tumor colon tissues and healthy controls from two existing microarray datasets. ELN protein was measured in human normal colon cells and colon cancer epithelial cells and tumor development was assessed in colon epithelial cells cultured in medium with or without ELN peptide on plates coated with ELN recombinant protein. Control plates were coated with PBS only.ResultsWe found ELN gene expression was increased in tumors from CRC patients compared to adjacent non-tumor tissues and healthy controls. ELN protein was increased in cancer cells compared to normal colon epithelial cells. Transforming growth factor beta (TGF-β) was a key cytokine to induce production of ECM proteins, but it did not induce ELN expression in colon cancer cells. Matrix metalloproteinase 9 (MMP9) gene expression was increased, but that of MMP12 (elastase) did not change between CRC patients and control. Tissue inhibitor of metalloproteinases 3 (TIMP3) gene expression was decreased in colon tissues from CRC patients compared to healthy controls. However, MMP9, MMP12 and TIMP3 proteins were increased in colon cancer cells. ELN recombinant protein increased proliferation and wound healing in colon cancer epithelial cells. This had further increased in cancer cells incubated in plates coated with recombinant ELN coated plate and in culture media containing ELN peptide. A potential mechanism was that ELN induced epithelial mesenchymal transition with increased alpha-smooth muscle actin and vimentin proteins but decreased E-cadherin protein. Tumor necrosis factor alpha (TNF) mRNA was also increased in CRC patients compared to controls. ELN recombinant protein induced further increases in TNF protein in mouse bone marrow derived macrophages after lipopolysaccharide stimulation.ConclusionsThese data suggest ELN regulates tumor development and the microenvironment in CRC.

Humanization of Tumor Stroma by Tissue Engineering as a Tool to Improve Squamous Cell Carcinoma Xenograft.

The role of stroma is fundamental in the development and behavior of epithelial tumors. In this regard, limited growth of squamous cell carcinomas (SCC) or cell-lines derived from them has been achieved in immunodeficient mice. Moreover, lack of faithful recapitulation of the original human neoplasia complexity is often observed in xenografted tumors. Here, we used tissue engineering techniques to recreate a humanized tumor stroma for SCCs grafted in host mice, by combining CAF (cancer associated fibroblasts)-like cells with a biocompatible scaffold. The stroma was either co-injected with epithelial cell lines derived from aggressive SCC or implanted 15 days before the injection of the tumoral cells, to allow its vascularization and maturation. None of the mice injected with the cell lines without stroma were able to develop a SCC. In contrast, tumors were able to grow when SCC cells were injected into previously established humanized stroma. Histologically, all of the regenerated tumors were moderately differentiated SCC with a well-developed stroma, resembling that found in the original human neoplasm. Persistence of human stromal cells was also confirmed by immunohistochemistry. In summary, we provide a proof of concept that humanized tumor stroma, generated by tissue engineering, can facilitate the development of epithelial tumors in immunodeficient mice.