Influence of host defenses on the hepatic colonization of B16F10 melanoma cells

Abstract

To investigate the significance of host immunity in metastasis we have simultaneously evaluated metastatic development and the tumoricidal action of host defenses in an experimental system for liver metastasis which involves the intrasplenic injection of B16F10 melanoma cells in syngeneic mice. In addition, three experimental groups were treated with immunosuppressive doses of cyclosporin A (CsA) during the following periods of the malignant process: 1st-5th days, 1st-12th days and 7th-12th days. Analysis of cytolytic effects of macrophages, NK cells and T-lymphocytes on tumor cells reveals a decay in antitumor immunity from the 7th day to the 12th day and a marked resistance of B16F10 melanoma cells derived from hepatic metastases to T-lymphocytes and NK cells. The 1st-5th day CsA treatment of tumor-bearing mice produced a reduction in both T-lymphocyte and macrophage reactions against tumor cells and a significant increase in the 7th day micrometastasis incidence in the liver. Once micrometastases have been established the CsA-treatment suppression on the 5th day allows the tumor growth rate in these mice to become the same as in controls. However, the 7th-12th day CsA treatment produces a clear inhibitory effect on focal metastatic development which may correspond to the in vitro antiproliferative effect of CsA, detected on cultured B16F10 melanoma cells.

Enhancement of la Antigen Expression and Nonproliferating Cells Correlates with Metastatic Capacity

“…To test this, single B16F10 melanoma cells in stirring culture or monolayer were injected intrasplenically [23,24], The number of tumor colonies recorded 7 days after inoculation shows a signifi cant increase in clonogenic potential (table 1). These re sults suggest that despite the biological difference between the two tissue microenvironments studied, stirring culture induces certain qualities in tumor cells which allow them to achieve metastatic colonization with more success.…”

“…Experimental hepatic métastasés were produced according to the method described previously [23], Briefly. C57BL/6 mice were anes thetized with an intraperitoneal injection o f sodium pentobarbital (50 mg/kg body weight).…”

Cyclosporin A Upmodulates the α-Subunit of the Interleukin-2 Receptor and the Metastatic Ability of Murine B16F10 Melanoma Cells

“…From a clinical point of view, the most important activity of CsA is probably the suppression of humoral and cell-mediated immune responses. In this sense, in a previous study we demonstrated that CsA treatment of B16F10 tumor-bearing mice produced a reduction in both T-lymphocyte and macrophage reactions against tumor cells and a significant increase in the 7th day 131 micrometastasis incidence in the liver [24]. More recently, in murine colon 38 tumor cells, Yokoyama et al [22] have shown that CsA enhances proliferation of hepatic metastasis in vivo.…”

“…In the case of the B16F10 melanoma, we have shown that CsA treatment during the early neoplastic period enhances the implantation of micrometastasis in the liver coinciding with the lowering of both T lymphocyte and macrophage reactivity [24].…”

“…Metastatic colonies in the lungs were counted under the dissection microscope. Experimental hepatic metastases were produced according to the method described previously [24]. A standard inoculum of 5 !…”