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

Abstract

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.

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

“…The use of an adequate number of CSCs remains an important aspect, as is a matrix that supports precise implantation of cells in the exact inoculation site. Matrigel is the most used enriched matrix in experiments [ 151 , 152 ].…”

Scientific Research Directions on the Histopathology and Immunohistochemistry of the Cutaneous Squamous Cell Carcinoma: A Scientometric Study

“…For assessing the impact of and to establish the research directions for squamous cell carcinomas, we used the scientometric method [ 3 , 4 ]. A set of instructions was defined based on the keywords from the 76 articles we assessed [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , …”

Updates of Role of Stem Cells in Cancer Therapy

“…The utilization of adequate number of CSCs stays a significant viewpoint, similar to a matrix that supports precise implantation of cells in the specific inoculation site. Matrigel is the most involved enriched matrix in experiments [146,147]. The focus ought to be on fibroblasts within TME (tumor microenvironment) representing the "stromal bed" in the central part of the tumor.…”