A novel experimental platform for investigating cancer growth and anti-cancer therapy in a human tissue microenvironment derived from human embryonic stem cells.
There is no available experimental system wherein human cancer cells can be grown in the context of a mixed population of normal differentiated human cells for testing biological aspects of cancer cell growth (tumor cell invasion, angiogenesis) or response to anti-cancer therapies. Human embryonic stem cells when implanted into immunocompromised mice develop teratomas containing complex structures, comprising differentiated cell types representing the major germline-derived lineages. We sought to determine whether human cancer cells would grow within such teratomas and display properties associated with malignancy such as invasiveness and recruitment of blood vessels. Ovarian cancer cells (HEY), stably expressing an H2A-GFP fusion protein, which allows tracking of tumor cells, were injected into mature teratomas and developed into tumors. The growth, proliferation capacity, invasion, and induction of blood vessel formation were examined. We propose using the novel experimental platform we have described, consisting of human tumor cells growing within a human cellular microenvironment derived from human embryonic stem cells, to develop a preclinical model for investigating and manipulating the stromal response in tumor cell growth, as an additional tool in cancer research.
Tzukerman
Maty
M
Rappaport Research Institute, Haifa, Israel.
Skorecki
Karl L
KL
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000302:isolation & purification; D005260:Female; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000628:therapy; D010957:Plasmids; D039904:Pluripotent Stem Cells / Q000166:cytology*; D012334:RNA, Neoplasm / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013724:Teratoma / Q000473:pathology* / Q000628:therapy; D014162:Transfection / Q000379:methods; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D049452:Green Fluorescent Proteins