Macrophages in cancer metastases and their relevance to metastatic growth

Abstract

The dissemination of malignant cells throughout the body to form secondary growths is a highly complex process dependent upon both host and tumor cell properties. One potential defensive system which could influence the outcome of metastasis is the mononuclear phagocyte system. Although macrophages have been observed in essentially all primary and metastatic tumors examined regardless of histologic type or anatomic location, the biological significance of these observations is far from clear. What is clear, however, is that in most cases the effects of macrophages on tumor cells are not sufficient to alter progressive growth. Therefore, the presence of macrophages within metastases does not necessarily signify a protective host defensive response. On the other hand, macrophage-induced regression of established metastases can occur in vivo under certain conditions in which tumor-bearing mice are treated systemically with macrophage-activating agents. When mice bearing metastases are treated with macrophage-activating agents contained within liposomes, metastasis-associated macrophages are activated to the tumoricidal state and the metastatic lesions are simultaneously eradicated. Such a process of macrophage activation may have implications in determining successful approaches to the therapy of disseminated cancer.

Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis

“…Tumors are generally associated with hypoxia and the infiltration of inflammatory cells (22,23). Thus, it is reasonable to hypothesize that this negative feedback system might not operate efficiently in tumors.…”

“…Regarding hypoxia, we analyzed about 5 kb upstream of the 5′ flanking region of the vasohibin gene, but we did not find any consensus sequences of hypoxiaresponsive elements. Nevertheless, it is well known that tumors are associated with hypoxia as well as the infiltration of inflammatory cells (22,23). Therefore, this negative feedback system may not operate efficiently in tumors.…”

Effects of L2C leukemia on macrophage-mediated responses

“…Macrophages have shown to actively invade solid tumors [15,18] and have cytotoxic activity against a variety of tumor cells [10,18,19,28,33]. Macrophages also have been implicated variously in potentiating [9,13] or inhibiting metastatic potential [10,11,15,17].…”

“…Amarillo, TX 79106, USA Studies in other tumor systems have shown that macrophages are necessary for the stimulation of antitumor immunity [33], and that a normal macrophage population is necessary for adoptive transfer of antitumor immunity by lymphoid cells [34]. Macrophages may contribute to lymphocyte-mediated antitumor immunity by presentation of tumor antigen and elaboration of interleukin-1 (IL-1) [22,24], or they may be directly cytotoxic to tumor cells after activation [15,19,25,31]. Macrophages have shown to actively invade solid tumors [15,18] and have cytotoxic activity against a variety of tumor cells [10,18,19,28,33].…”

“…Macrophages may contribute to lymphocyte-mediated antitumor immunity by presentation of tumor antigen and elaboration of interleukin-1 (IL-1) [22,24], or they may be directly cytotoxic to tumor cells after activation [15,19,25,31]. Macrophages have shown to actively invade solid tumors [15,18] and have cytotoxic activity against a variety of tumor cells [10,18,19,28,33]. Macrophages also have been implicated variously in potentiating [9,13] or inhibiting metastatic potential [10,11,15,17].…”