A histopathological investigation of the host inflammatory response and tumour invasion into host tissues following transplantation of ascites tumours within murine hosts
The LAC and EL4 ascites tumour cells contained both Type A and Type C virions. These virions replicated within the ascites tumour cells. However, neither the tumour cells nor their murine hosts were contaminated with LDV virions. Intraperitoneal transplantation of the LAC and EL4 ascites tumours provoked an oedematous inflammatory response which was accompanied by histological changes within the lymphoid organs of their hosts. Intraperitoneal transplantation of the LAC tumour within MF1 mice induced histopathological changes within the spleens and mediastinal lymph nodes compatible with an immune response. Intraperitoneal transplantation of the EL4 ascites lymphoma within C57BL10 mice culminated in infiltration of EL4 cells into both the spleen and mediastinal lymph nodes. Both the LAC and EL4 ascites tumours induced thymic involution and inflammation within the livers of their murine hosts. Growth of the LAC and EL4 ascites tumours within the peritoneal cavity was accompanied by infiltration of ascites tumour cells into the adipose tissues, pancreas, diaphragm and mesenteries. Whereas successful transplantation of the EL4 ascites lymphoma was achieved in both intraperitoneal and subcutaneous locations, the LAC tumour was only transplanted successfully intraperitoneally but not in subcutaneous locations. Subcutaneous transplantation of EL4 cells within the hind limbs of C57BL10 mice provoked an inflammatory response culminating in angiogenesis and fibroplasia around the transplants. As the growing transplants invaded the surrounding host tissue there was extensive remodelling of the connective tissue matrix followed by degradation of the connective tissue. Host inflammatory cells infiltrated the growing EL4 tumours but ultrastructural studies did not reveal any obvious indications that the host cells exerted an antitumour effect. Instead the macrophages appeared to phagocytose degraded materials within the tumours and therefore behaved as traditional phagocytes. The macrophages within the EL4 tumours had a well developed endoplasmic reticulum and Golgi apparatus, indicative of a secretory status for the cells, and it has been suggested that the macrophages within the EL4 tumours may have a trophic role. Any cytotoxic functions of the macrophages may have been suppressed by tumour derived or host cell derived factors generated within the complex ecosystem of the EL4 tumours. Subcutaneous transplantation of LAC cells within the hind limbs of MF1 mice did not provoke an intense inflammatory response and angiogenesis and fibroplasia was not apparent around the tumours soon after transplantation. It has been speculated that the LAC cells may have suppressed angiogenesis and fibroblast proliferation through production of anti-inflammatory factors. As a consequence of the lack of angiogenesis, the transplanted LAC cells necrosed and only then provoked an inflammatory response from their hosts. The inflammatory response resulted in the formation of scar tissue which gradually replaced the necrosed LAC cells at the site of transplantation. Intraperitoneal transplantation of LAC and EL4 ascites tumour cells provoked an inflammatory response. The inflammatory leucocytes did not appear to impair the viability of the LAC and EL4 cells and although the host inflammatory cells established contacts with the tumour cells they did not appear to sustain any damage and the transplants proliferated to establish ascites tumours. Within the MF1 mice some of the peritoneal macrophages appeared to be damaged and it is suggested that the LAC cells release a factor cytotoxic for macrophages. Within the C57BL10 mice ip injection of the EL4 cells provoked fibrin deposition and the fibrin was phagocytosed by the macrophages. During the course of tumour growth the LAC and EL4 cells bound alpha and gamma globulins to their sufaces and it is believed that these molecules may have afforded the ascites cells 'immunological protection' by masking cell surface antigenic determinants. During the course of the inflammatory response which attended the growth of the ascitic tumours the mesothelial cells covering the mesenteries and adipose tissue underwent a retraction response and exfoliated thus allowing the LAC and EL4 cells to invade these tissues. Whereas ip transplantation of LAC cells into normal MF1 mice resulted in the formation of ascites tumours, ip transplantation of LAC cells into mice which had already injected a subcutaneous transplant of LAC cells, resulted in rejection of the ip transplanted cells. Lymphocytes and macrophages participated in the rejection response and during the course of this event the macrophages became activated.