Kinetics of inflammation and sarcoma cell development in primary moloney sarcoma‐virus‐induced tumors

Abstract

The kinetics of "sarcoma" cell appearance and inflammatory cell infiltration into primary Moloney sarcoma virus (MSV>induced tumors has been studied in normal and partially immunosuppressed anti-lymphocyte-globulin (ALGPtreated W y S n mice. The ALG treatment facilitated an earlier appearance of gp7O-positive "sarcoma" cells accompanied by an intense inflammatory response. Time course pulse-labelling studies showed that a decreasing proportion of gp7O-positive "sarcoma" cells were incorporating ['HI-thymidine in vivo in both normal and immunosuppressed mice as the lesion progressed to maximum size. ALG-treated mice inoculated with MSV were given a single injection of ['HI-thymidine immediately prior t o extensive appearance of gp7O-positive "sarcoma" cells (day 6) and were studied for the presence of labelled gp7O-positive cells 2 h, 2 days and 6 days post labelling. The data indicate that few cells divided during the time in which an 8-to 10-fold increase in virus-positive "sarcoma" cell number occurred. These experiments provide evidence that recruitment rather than proliferation of virus-positive cells occurred. The results also suggest that, within the tumor, defense mechanisms develop which restrict sarcomacell proliferation also in ALG-treated mice. The composition of inflammatory cells during the course of tumor progression and regression in the uncompromised mice revealed that the proportion of lymphocytes was highest early and late during tumor development, dropping to a minimum at the peak size of the tumor.Macrophages and granulocytes constituted 70-80 YO of the total cells recovered at peak tumor size and the onset of regression. In the ALG-treated mice, the proportions of macrophages, granulocytes, and infrequent lymphocytes remained constant throughout the duration of the tumor progression. A decrease in total cells, including a decrease in gp7O-positive cells, was noticed before a change in the proportion of infiltrating lymphocytes occurred due to recovery of the immune system. The composition of the inflammatory cells at onset of regression suggests that macrophages and granulocytes are of major importance in the defense against MSV infection.

Immunopathology

“…Similar quantitation of intra tumoral inflammatory cells was obtained by Russell et al (1976a). Becker and Haskill (1981) found that macrophages and granulocytes predominated through the stages of tumor growth and early regression, implying that these cells played some role in the host defense. This is supported by the fact that in ALS-treated animals, where the tumors also eventually regressed, the intratumoral inflammatory infiltrate was exclusively composed of these cells.…”

Indomethacin Influences Moloney's Sarcoma and Associated Periosteal Osteogenesis in the Mouse

“…Recently, it was reported that in mice transplanted tumor cells of various origin induce periosteal osteogenesis (Wlodarski and Reddi 1987). Some authors suggest that Mu-MSV-induced tumor is not a true neoplasm, but merely an inflammatory reaction against virus-infected cells (Becker and Haskill 1981). However, this suggestion is negated by the in vitro establishment of a murine Moloney sarcoma cell line MSVC (Wlodarski et al 1986), which produces tumors that upon transplantation into host animals regress slower than virus-induced tumors.…”