Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 103, Issue 9, Pages 3351-3356Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0511306103
Keywords
endosialin; metastasis; stroma; tumor invasiveness; angiogenesis
Categories
Funding
- NCI NIH HHS [P50 CA062924, CA62924, CA57345, R01 CA057345, R37 CA057345] Funding Source: Medline
- NCRR NIH HHS [RR00171, K26 RR000171] Funding Source: Medline
- NIGMS NIH HHS [GM07184, GM07309, T32 GM007184, T32 GM007309] Funding Source: Medline
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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.
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