A Novel In Vitro System to Study Extravasated Tumor Cell-Induced Angiogenesis


1Biological Sciences Department, Wayne State University, Detroit, USA
2Karmanos Cancer Institute, Detroit, USA
3Gershenson Radiation Oncology Center, Detroit, USA


Angiogenesis, the formation of new blood vessels from preexisting ones, is a fundamental stage in the metastatic pathway. For the primary tumor, this neovascularization provides nutrients and oxygen as well as a route by which metastatic tumor cells gain access to the circulatory system. Among these metastatic tumor cells, there are subgroups of cells that express an angiogenesis-inducing cells phenotype (AICs) as well as others that do not. Tumor cells not expressing the angiogenesis-inducing cells phenotype (non-AICs) invade new tissues and remain as dormant micrometastases unless they accompany AICs. Thus, either alone or with non-AICs, angiogenesis-inducing cells form rapidly growing, clinically detectable metastases. Much of the current research in this area is concentrated on the vascularization of primary tumors, but the regulation of angiogenesis by extravasating or invading tumor cells has not being extensively studied. We have developed a working model, which demonstrates that human metastatic prostate cancer cells (PC-3) appear to induce human vascular endothelial cells (HUVECs) to translocate across a Matrigel-coated 8 ?m membrane. The parameters of this model (i.e. pore size, seeding-cell density, seeding times) were established using highly invasive murine melanoma cells (B16F10) seeded on murine microvascular endothelial cells (CD3). We have further modified our model in order to include a host compartment made of collagen gel, in order to mimic the in vivo site of metastases-induced angiogenesis. Pathology & Oncology Research, Vol 4, Nr 3, 225-229, 1998

Key words: blood vessels; collagen gel; extravasation; invasion; in vitro; metastasis; secondary angiogenesis

Received: May 25, 1998; accepted: Aug 12, 1998
Correspondence: John D TAYLOR, Biological Sciences Department, Wayne State University, 5047 Gullen Mall Detroit 48202, USA; Tel: 1-313-577-6816, Fax: 1-313-577-1093; E-mail:

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