Enhancement of tumor growth by basement membrane: Modulation of growth and angiogenesis by laminin-derived synthetic peptides

The study of human cancers has been impaired by a lack of good animal models. Human cancers are difficult to grow in culture, and the use of immunologically deficient mice has had limited success in propagating human tumors [1]. If a tumor is able to grow in a mouse, its ability to subsequently survive in culture is enhanced. We and others have found much greater take and growth of both murine and human tumor cells and primary isolates in mice when the cells are premixed with a basement membrane extract (Matrigel) and injected subcutaneously [2, 3, 4, 5]. In addition, we have been able to further increase the growth of solid tumors by the inclusion of a synthetic angiogenic peptide derived from the laminin A chain [6]. In contrast, anti-angiogenic peptides reduce the tumor growth even when intra-peritoneal injections of the peptide are initiated several days after tumor growth has begun [3]. Although these subcutaneous tumors do not frequently metastasize, the growth of such tumors is an important first step in developing animal models to study the metastatic and phenotypic properties of human cancer.