A unique complement derived chemotactic factor for tumor cells.

Abstract

A factor chemotactic for Walker carcinosarcoma and Novikoff hepatoma tumor cells can be generated by incubation of serum with an extract from tumor cells. The chemotactic factor has no activity for neutrophilic leukocytes, and three factors chemotactic for leukocytes are not chemotactic for tumor cells. By the use of complement deficient serums as well as purified cowplement components, the chemotactic factor for tumor cells has been found to be a fragment of the fifth component (C5) of complement and appears to result from direct interaction of C5 with an enzyme in the extract. The chemotactic factor for tumor cells can be classified as a functionally unique fragment of C5 that may significantly influence the behavior of tumor cells in vivo.That malignant tumor cells in the circulation do not necessarily result in the development of metastatic foci is a reasonably well-established observation (1). Considerable work has centered on mechanisms that might account for the extravascular localization of tumor cells. Various mechanisms, including "invasiveness" of tumor cells, the role of coagulation factors, and increased locomotive activity of tumor cells, to name only a few, have been postulated (2-4). In many respects the ability of malignant cells to pass from the blood stream into tissues resembles the behavior of leukocytes, which infiltrate tissues in response to inflammatory stimuli. Chemotactic mechanisms (defined as unidirectional migration induced by a concentration gradient of attractant) have been strongly implicated in cellular inflammatory responses, as demonstrated by the obligatory presence of chemotactic factors in developing reactions that become leukocyte-rich (5-7), and by the recognition that inadequate cellular inflammatory responses result from conditions in which either leukocytes are unable to respond to chemotactic stimuli or there is defective generation of chemotactic factors (6).It seems possible that migration of tumor cells from the blood stream into extravascular locations might also be a response to chemotactic stimuli specific for tumor cells. Indeed, an extract from rat hepatoma AH 109A cells has been reported to be chemotactic for a variety of tumor cells, but this substance has no chemotactic activity for neutrophilic leukocytes (8). Injection of this extract into rat skin led to the development of metastatic nodules, emphasizing the potential biological importance of chemotactic factors in the localization of tumor cells from the blood stream (9). The studies reported in this communication confirm the ability of tumor cells to respond to chemotactic stimuli. They also indicate that a novel chemotactic factor for tumor cells is generated from the complement system. These findings suggest the possibility that complement products may significantly influence the migrational behavior of tumor cells in vivo. MATERIALS AND METHODSChemotaxis Assays. The chemotactic behavior of leukocytes and tumor cells in vitro was assessed by the use of micropore filters in the modified Boyde...

Enhancement of Human Cancer Cell Motility and Invasiveness by Anaphylatoxin C5a via Aberrantly Expressed C5a Receptor (CD88)

“…Rather, they seemed not to be C5a because of its molecular weight and lack of chemotactic activity for leukocytes (35,36). When these studies were conducted, the C5aR molecule had not been identified, and neither recombinant C5a nor C5aR-specific antibodies were available to prove the activity of C5a to enhance cancer cell migration.…”

Collagen and Collagen-derived Fragments Are Chemotactic for Tumor Cells

“…which were originally derived from a spontaneous rat breast tumor and are maintained by serial passage in cell culture. Chemotactic behavior of these cells has been described in detail previously (2)(3)(4)(5)(6). HeLa cells that were originally derived from a patient with carcinoma of the cervix were obtained from Dr. T. Schenk.…”

“…The technique for studying both leukocyte and tumor cell chemotaxis in vitro has been described in detail previously (1)(2)(3)(4)(5)(6). In brief, cultured tumor cells that are removed by mechanical dispersion are placed in the upper compartment of a modified Boyden chamber at a concentration by 5 x 105 cells/ ml of culture medium.…”

The First Fifty Years in Research

“…We also discovered that a subfragment of C5a was chemotactic for tumor cells (26)(27)(28)(29)(30)(31), suggesting that-like blood leukocytes in the inflammatory response-tumor cells also emigrate from the blood in a similar manner, responding to tissue-induced chemotactic factors and apparently originating from C5 (27). Based on these findings, the metastatic process for tumor cells could be seen as a form of inflammatory response involving the adherence and transmigration of circulating tumor cells.…”