Influence of dispase and angiogenesis factors on the growth of human xenografts.

Abstract

The growth development of a human adenocarcinoma, derived from the sigmoid colon and heterotransplanted to athymic, nude mice, was observed after pretreatment of the assigned site of transplantation (a) with the neutral protease dispase, (b) with angiogenic factors, such as prostaglandin E1 (PGE1) and phorbol 12-myristate 13-acetate (PMA), (c) with endothelial cell growth factor, or (d) with homogenized tumor material. The substances or preparations were applied several times within 1, 2, 3 or 4 days before tumor transplantation to nude mice. Following pretreatment with dispase or PGE1, tumor development was accelerated as a function of the doses and regimens applied, whereby the initial events after tumor transplantation, consisting of the removal of necrotic tumor cells and the invasion of host-supplied connective tissue into the xenografts, were obviously accelerated, resulting in an earlier beginning of exponential tumor growth. On days 25 and 28, the volumes of tumors pretreated with dispase or PGE1 exceeded those of control tumors by factors of between 3 and 5. Whereas applications of the phorbol ester PMA or endothelial growth factor did not influence tumor development, pretreatment with homogenized tumor material also effected acceleration of tumor development by about 7 days and increases of the final tumor volume by factors of between 2 and 3. These results underline the stimulating function of host-supplied connective tissue for the development of xenografted human tumors and open new perspectives to influence the growth velocity and, possibly, also the take-rates of human tumors in nude mice.