Macrophage infiltration and growth of sarcoma clones expressing different amounts of monocyte chemotactic protein/JE

Abstract

Tumor-derived chemotactic factors (TDCF) have been identified and thought to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of the TDCF molecularly identified as monocyte chemotactic protein/JE, by investigating murine sarcoma clones expressing different levels of MCP/JE. The 1D3 clone derived from the B77 RSV-induced sarcoma expressed appreciable levels of MCP/JE mRNA and, concomitantly, chemotactic activity for mononuclear phagocytes. In contrast, the 5B11 clone from the same tumor had undetectable levels of MCP/JE transcripts and little or no chemotactic activity. The chemotactic activity of 1D3 cells was blocked by an appropriate specific antiserum. The in vitro growth rate of the 2 sarcoma lines was identical. Upon in vivo transplantation, the 1D3 clone showed a substantially higher level of tumor-associated macrophages (28.9%; range 21%-34%) than the 5B11 clone (16.6%; range 13%-20%). 5B11-induced tumors appeared earlier and grew faster than those induced by 1D3. The difference in growth rate and in macrophage infiltration between 1D3 and 5B11 clones was also evident upon transplantation into nude mice. These results are consistent with the hypothesis that TDCF, identified as MCP/JE, is one important determinant of macrophage infiltration in tumors.

Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases

“…On the other hand, tumorassociated leukocytes, particularly macrophages, may be a potential source of growth factors for tumor cells and endothelial cells. Thus chemokines with chemotactic activities for monocytes/macrophages, particularly CCL2, are presumed to be involved in tumor progression by recruiting and activating macrophages to produce growth factors (157). In bronchoalveolar carcinoma, tumor cells are a main source of CXCL8, and neutrophils are located mainly in the alveolar lumen, whereas lymphocytes are exclusively in the alveolar wall.…”

A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF- B and enhanced IRF-3/STAT1 activation)

“…13,14 The present study was designed to characterize the transcriptional profile of TAMs obtained from a murine sarcoma 11 where these cells exert a protumor function. 15 The transcriptional program of TAMs was compared with those expressed by peritoneal macrophages (PECs) and myeloid suppressor cells (MSCs). PECs and TAMs are mature macrophage populations originating from common precursors, the circulating monocytes, whereas MSCs represent a prototypical M2 myeloid population.…”

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma

“…This process is RANKL-dependent and is of interest with regard to tumour osteolysis associated with Ewing's sarcoma as TAMs form a significant inflammatory component of rapidly growing malignant tumours (Bugelski et al, 1987;Walter et al, 1991;Mantovani et al, 1992;Van Ravenswaay et al, 1992).…”