To determine if MH S conditioned media directly stimulates neoplastic growth, we first evaluated neoplastic colony formation and cell number after long term conditioned media exposure. In both the classic model of anchorage inde pendent neoplastic growth on soft agar, and colonization on new ultra low adherence, neu trally charged plastic, KOS 953 macrophage con ditioned media potently stimulated the proliferation of two Kras mutant lung tumor derived cell lines. Thus, macrophages secrete soluble mole cules capable of greatly stimulating neoplastic colony formation and proliferation in vitro, which may shed light on the role of macrophage recruitment to lung cancer in vivo. Na ve and tumor educated primary macrophage co culture Inhibitors,Modulators,Libraries stimulates the proliferation of neoplastic and non neoplastic pulmonary epithelial cells The relative ability of na ve vs.

tumor educated alveolar macrophages to directly stimulate lung epithelial cell proliferation not been reported. To determine if macro phages from the lungs of tumor bearing mice could directly stimulate neoplastic cell Inhibitors,Modulators,Libraries growth in a co culture system, Inhibitors,Modulators,Libraries neoplastic LM2 cells were co cultured with bronchoalveolar lavage macrophages iso lated from tumor bearing mice, and monolayer growth was assessed. Growth in standard tissue cul ture conditions measures proliferation per se, and not cell motility or the requirement for solid support, and permits the evaluation of non neoplastic epithelial cells which do not proliferate in anchorage independent sys tems. LM2 cell number significantly increased with BAL macrophage co culture at 48 and 72 hrs.

Inhibitors,Modulators,Libraries As 72 Inhibitors,Modulators,Libraries hrs selleckchem Cisplatin of macro phage co culture resulted in 2 times more tumor cells, this time point was used in subsequent experi ments. To determine if tumor educated macrophages stimulated neoplastic growth more effectively than na ve, BAL macrophages from either na ve or tumor bearing mice were co cultured with neoplastic LM2 and JF32 cells. LM2 growth was equally stimulated by both na ve and tumor educated BAL macrophages, while the growth of JF32 cells was enhanced slightly upon co culture with tumor educated BAL macrophages. To determine if primary alveolar macrophages also stimulated the proliferation of non tumor cells, the non neoplastic E10 cell line was co cultured with na ve and tumor educated BAL macro phages. Both macrophage types increased E10 cell num ber 3. 5 fold when maintained in serum free conditions. only tumor educated macrophages stimu lated E10 proliferation when cultured in the presence of serum. Both types of primary macrophages equally stimulated LM2 proliferation in the presence of serum, though the magnitude was reduced when com pared to serum free co culture.