Tumor endothelial marker 1 (Tem1) Functions in the Growth and Progression of Abdominal Tumors

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-02, Vol.103 (9), p.3351-3356
• Main Authors: Nanda, Akash, Karim, Baktiar, Peng, Zhongsheng, Liu, Guosheng, Qiu, Weiping, Gan, Christine, Vogelstein, Bert, Croix, Brad St, Kinzler, Kenneth W., Huso, David L.
• Format: Article
• Language: English
• Subjects: Abdominal Neoplasms - blood supply; Abdominal Neoplasms - genetics; Abdominal Neoplasms - metabolism; Abdominal Neoplasms - pathology; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Biological Sciences; Biology; Biomarkers, Tumor - deficiency; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell growth; Disease Progression; Endothelial cells; Epithelial cells; Female; Gene expression; Genotypes; Humans; Liver; Medical research; Metastasis; Mice; Mice, Knockout; Neoplasm Proteins - deficiency; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Proteins; Rodents; Stromal cells; Tumors; Wound healing; Xenograft Model Antitumor Assays
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0511306103

Tumor endothelial marker 1 (Tem1; endosialin) is the prototypical member of a family of genes expressed in the stroma of tumors. To assess the functional role of Tem1, we disrupted the Tem1 gene in mice by targeted homologous recombination.$Tem1^{-/-}$mice were healthy, their wound healing was normal, and tumors grew normally when implanted in s.c. sites. However, there was a striking reduction in tumor growth, invasiveness, and metastasis after transplantation of tumors to abdominal sites in mice without functional Tem1 genes. These data indicate that the stroma can control tumor aggressiveness and that this control varies with anatomic site. Therefore, they have significant implications for the mechanisms underlying tumor invasiveness and for models that evaluate this process.