Metastasis: Reticuloendothelial system and organ retention of disseminated malignant cells

Abstract

The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125l]dUrd-labelled tumor cells into B16 melanomabearing mice. Experiments were performed with mice undergoing acute or chronic reactions to bacterial endotoxin or zymosan, both of which were shown to modify the activity of the reticuloendothelial system as assessed by carbon clearance assays. On the one hand, the release of arrested melanoma cells from the lungs was retarded in mice with both endotoxin-and zymosan- induced acute inflammation. There was a parallel increase in the numbers of pulmonary tumor nodules which developed after injection of non-radiolabelled melanoma cells into similarly treated groups of mice. On the other hand, fewer tumor cells were retained in the lungs of mice undergoing chronic responses to endotoxin, and fewer pulmonary tumor nodules subsequently arose after injection of unlabelled cells. However, in mice pre-treated with zymosan, retention of melanoma cells was not different from that in controls and greatly increased numbers of pulmonary nodules grew in zymosan pre-treated mice receiving non-radiolabelled cells. These experiments were discussed in terms of the contribution of the reticuloendothelial system to the release of arrested cancer cells from the pulmonary vasculature.

Correlation between circulating cancer cells and incidence of metastases

“…However, as shown by the present and previous observations (Fidler, 1970;Glaves, 1980;Weiss, 1980) In conclusion, these studies provide quantitative data on spontaneous cancer cell input into the metastatic cascade. They also identify particular points in the cascade at which two tumours with different metastatic frequencies diverge in their behaviour.…”

“…Tumour cell aggregates have previously been shown to generate disproportionately more lung colonies than equivalent numbers of single cells after tail-vein injections (Liotta et al, 1976;Fidler, 1973) and the yield of spontaneous metastases was also related to the release of clumps from T241 fibrosarcomas (Liotta et al, 1974 (Fidler et al, 1977;Weiss & Glaves, 1976) and non-specific defence factors (Glaves, 1980;Riccardi et al, 1979) involved in clearance of arrested cancer cells from the lungs.…”

Quantitation of tumorigenic disseminating and arrested cancer cells

“…The present study shows that this inefficiency is not related to the tumorigenic potential of cancer cells leaving the primary tumour. This emphasizes the importance of those active specific and non-specific defense processes (Weiss & Glaves, 1976;Fidler et al, 1977;Riccardi et al, 1979;Glaves, 1980) operating in the lungs which contribute to the death of as many as 98% of these two types of tumour cells within 24 h of their initial arrest (Glaves, 1983;Fidler et al, 1976 The numbers of circulating Lewis carcinoma cells quantified by bioassay were within similar ranges to those quantitated previously by direct counting techniques (Glaves, 1983) (Strauli et al, 1980), but this role can now be quantitatively assessed directly, in vivo, during spontaneous metastasis. …”

Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

“…To date, however, the absolute number of cells required for metastasis in the human circulation is unclear and even if cancer cells are detected in the circulation, their potential to develop metastatic foci is unknown. When malignant cells were released into the circulation, a variety of host and tumor cell factors could determine their distribution and fate [28][29][30][31][32][33] . Most circulating HCC cells may rapidly die in the blood by various host immune and non-immune defenses, and are destroyed by mechanical forces, including turbulence and the trauma associated with vascular adhesion and transcapillary passage, or lysed by lymphocytes, monocytes, and natural killer (NK) cells.…”

“…Some tumor cells are nonspecifically trapped or specifically arrested in the first capillary bed encountered. Circulating tumor cells trapped in a given location could then recirculate and arrest at other locations, then grow into tumor colonies [29][30][31][32][33] . Okuda et al [34] and Komeda et al [14] could not detect any hAFP gene transcripts in patients with liver metastases or in healthy persons.…”