The effects of tumor facilitating factor of B16 melanoma on the macrophage

B16 cells produce a tumor facilitating factor (TFF) that increases B16 tumor incidence in mice injected with a small number of B16 cells. TFF was derived from serum-free culture supernatant concentrated on an Amicon PM10 membrane. One milliliter of concentrated material represented the product 10(8) B16 cells during a 6-h incubation. We report data that indicate TFF may act by altering macrophage function. In the nude mouse deficient in T cell, but not macrophage function, the injection of 0.8 ml of TFF facilitated tumor development. Subcutaneous injection of 0.7 ml of TFF induced mouse peritoneal macrophages to spread when removed and plated on glass coverslips. This effect peaked 3 days after injection of TFF and was abrogated by heating the TFF to 70 degrees C for 1 h. The injection of TFF was also able to induce macrophage spreading in nude mice. Injection of viable B16 cells induced spreading, as would be predicted if TFF is produced by B16 cells in vivo. In vitro incubation of peritoneal cells with TFF was also able to induce macrophage spreading. Finally, subcutaneous injection of TFF reduced by 80% the accumulation of peritoneal cells in response to intraperitoneal injection of phytohemagglutinin. We suggest that one mode by which TFF facilitates tumor growth is by reducing the numbers of macrophages chemotaxing to the tumor site.