Metastasis of xenogeneic and allogeneic tumors in nude mice

Abstract

Understanding the pathogenesis of cancer metastasis is fundamental to the design of successful therapeutic modalities for treatment of disseminated cancer. Metastasis development is determined by both host factors and intrinsic properties of the tumor cells [1]. To establish metastases, tumor cells must invade the surrounding local tissue and eventually penetrate into blood vessels and/or the lymphatic system. In the circulation, they must survive the potentially lethal interaction with host defense mechanisms, be arrested in the capillary bed of distant organs, extravasate into organ parenchyma, vascularize, and proliferate to form distinct foci of metastatic tumor growth [2–4]. Interruption of the sequence at any of these steps can inhibit metastasis formation. It is, therefore, not surprising that modification of either host factors or tumor cell properties influences the outcome of tumor dissemination and the establishment of distant organ metastases [5–8]. Host immune mechanisms (specific and nonspecific; natural and acquired) can intervene at different stages of the metastatic process and, thereby, inhibit the development of visible clinical metastases [9–11]. Studies using animals with selective immune deficiencies have contributed considerably to the elucidation of the host factors involved in tumor metastasis [10, 12–14]. Such animal models also have potential for studies of effective therapy of metastasis. Unfortunately, studies of metastases of human malignant neoplasms have been hampered by a lack of adequate in vivo models.

Research sponsored by the National Cancer Institute Contract No. N01-C0–75380 with Litton Bionetics, Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.