Role of hypoxia in tumor cell adherence to endothelial cells

University Of Pennsylvania, Philadelphia PA

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Abstract

(Applicant's Abstract): Metastasis is the primary cause of morbidity and mortality from cancer. We have recently shown intravascular formation of metastasis in the pulmonary circulation from endothelium attached tumor cells, rather than from extravasated ones. These results exemplify the importance of tumor cell/endothelial cell interaction in the development of metastasis. It is not known whether tumor cell/ endothelial cell interaction is mediated by cell adhesion molecules as in the neutrophil-endothelial ell interaction. Squamous cell carcinoma of the head and neck often metastasize to the lungs via hematogenous spread. One of the goals of this project is to characterize the primary mechanisms of blood-borne metastasis of head and neck cancer in the lung in terms of tumor cell-endothelial cell interaction and modulation of this interaction by hyperbaric oxygen (HBO), since HBO has been shown to inhibit E12-integrin mediated neutrophil adherence. Although it can be postulated that HBO may lead to decreased metastasis due to prevention of tumor cell attachment to the endothelium, the net effect of HBO on the fate of metastatic cells would also depend on the effect of HBO on tumor cell growth. Some controversy still exists whether HBO has cancer causing or tumor growth promoting effect. Therefore, another goal of these studies is to characterize the effect of HBO on the growth of metastatic tumor cells in the lung vessels. These studies may not only lead to better understanding of the mechanisms of metastasis, but also help in the development of better HBO treatment regimens or cancer.