GROWTH AND METASTASIS OF HUMAN BREAST CANCERS IN ATHYMIC NUDE-MICE

To evaluate critically the merit of utilizing a wound model for growin g human tumors, a series of increasingly difficult human tumor types w ere tested for growth at sites of trauma in athymic nude mice. In vitr o tumor lines as well as fresh tumors from the breast, colon, rectum, lung, and a metastasis from an unknown primary were intraperitoneally injected into mice subjected to intra-abdominal organ injury. Successf ul xenografts were obtained from nine of 10 cell lines and 14 of 24 fr esh tumors. The latter included five of six (83%) colon cancers, one l ung tumor, metastatic tumor of unknown primary, three of four (75%) me tastatic breast cancers and four of six (67%) estrogen receptor (ER)-n egative breast primary tumors. Six ER-positive breast tumors tested fa iled to grow in mice without estrogen supplementation. Xenografts from two breast, two colon and the lung cancers formed spontaneous metasta ses and all xenografts tested were able to yield serial transplants in the surgical wound model. Histologically, all xenografts and their me tastases were identical to their respective donor tumors. Transplantab ility in mice without exogenous estrogen supplementation was linked to the absence of estrogen and progesterone receptors in breast tumors. Transplantability of the cell lines was associated with the expression of cell surface receptors for fibronectin and hyaluronic acid. Recept ors for other extracellular matrix components, namely, laminin, vitron ectin, collagen, fibrinogen or von Willebrand factor were not associat ed with transplantability. These results demonstrate that a large prop ortion of human tumors, including the breast tumors, can be successful ly xenografted into athymic mice by providing them with a healing woun d environment, and that such xenografts grown at ectopic sites exhibit metastatic ability.