title: Reconstitution of a metastatic-resistant tumor microenvironment with cancer-associated fibroblasts enables metastasis.
abstract: The tumor microenvironment is critical for metastasis to occur. Subcutaneous xenografts of tumors in immunodeficient mice are usually encapsulated and rarely metastasize as opposed to orthotopic tumors which metastasize if the original tumor was metastatic. In the present report, we were able to reconstitute a metastatic tumor microenvironment by subcutaneously co-transplanting a human cervical cancer cell line and human cervical cancer-associated fibroblasts (CAFs), in athymic mice, which resulted in lymph node metastasis in 40% of the animals. In contrast, no metastasis occurred from the cervical cancer without CAFs. These results suggest that CAFs can overcome an anti-metastatic tumor environment and are a potential target to prevent metastasis.
authors.affiliation: a Dept. of Obstetrics and Gynecology Kawasaki Medical School , Okayama , Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Murata
authors.affiliation: b Dept. of Cell Biology , Research Institute for Microbial Diseases, Osaka University , Osaka , Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Mekada
authors.affiliation: c AntiCancer, Inc. , San Diego , CA , USA.|d Department of Surgery , University of California San Diego , CA , USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008819:Mice, Nude; D040521:Subcutaneous Tissue / Q000473:pathology; D059016:Tumor Microenvironment
keywords: GFP; cancer-associated fibroblasts; cervical cancer; imaging; metastasis; nude mice; subcutaneous transplant