Studies on the mechanisms of invasion in cancer. II. <i>In vivo</i> effects of a factor chemotactic for cancer cells

Ozaki, Teruhisa; Yoshida, Keishiro; Ushijima, Kenichiro; Hayashi, Hideo

doi:10.1002/ijc.2910070111

Cited by 59 publications

(17 citation statements)

References 7 publications

(5 reference statements)

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“…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.…”

supporting

confidence: 66%

A unique complement derived chemotactic factor for tumor cells.

Romualdez¹,

Ward²

1975

Proc. Natl. Acad. Sci. U.S.A.

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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...

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supporting

confidence: 66%

A unique complement derived chemotactic factor for tumor cells.

Romualdez¹,

Ward²

1975

Proc. Natl. Acad. Sci. U.S.A.

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“…found to promote extravascular emigration of tumor cells (Ozaki et al, 1971) may be of importance in selective metastasis and may relate to Pilgrim's suggestion (Pilgrim, 1972) that tumor cells "home in" to organs comprised of similar cell type. Thus reticulum sarcoma cells might be expected to metastasize selectively to the spleen which has a high reticuloendothelial cell population.…”

Section: Discussionmentioning

confidence: 88%

Preferential splenic metastases in parabiotic animals

Schour

Faraci

1974

Journal of Surgical Oncology

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A reticulum cell sarconia which metastasizes preferentially to the spleens of inbred C, H mice has been studied. Placement of tumor-bearing animals in parabiosis with normal animals was followed by the development of gross metastases limited to the spleen in 100% of the normal animals. The pattern of metastases observed when a tumor-bearing animal was placed in parabiosis with a splenectomized animal is described. The splenotrophic tendencies of this tumor and its ability to metastasize selectively across a parabiotic union provide a model for investigation of the role of immunity and humoral factors in tumor metastases.

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“…1) and there is ample evidence that exposure of cultured basement membranes facilitates adhesion of cancer cells [14,28]. However, it has not been clearly demonstrated that retraction is responsible for increased metastasis after endothelial injury in vivo and there are data suggesting that injection of local or systemic vasopermeability factors (putative effectors of endothelial retraction) does not alter the metastasis of cells injected into the circulation [29,30].…”

Section: Involvement Of Oxygen-derived Free Radicals In Metastasismentioning

confidence: 99%

Cancer cell interactions with injured or activated endothelium

1992

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Blood vessels and lymphatics are the most important pathways for dissemination of cancer cells but the entry and exit of these cells into and from the vasculature requires that they pass through barriers formed by the endothelium and its basement membrane. This review summarizes evidence that this step in metastasis can be regulated by microenvironmental influences which alter the properties of this barrier. These phenomena can be attributed to both 'passive' and 'active' responses of the endothelium. The microvasculature is susceptible to perturbation from environmental agents, host cells and cancer cells. There is clinical and experimental evidence that this can upregulate the metastatic process. Using established animal models of pulmonary microvascular injury it has been shown that endothelial damage promotes the localization and metastasis of circulating cancer cells to the lung and that this effect is lost after endothelial repair. Oxidative stress is an effector of vascular damage in several of the experimental models. While endothelial cells appear to be directly susceptible to free radical attack, basement membranes are not. However, oxidative injury of endothelial cells causes release of proteases which can then degrade the basement membrane. This event is associated with generation of tumor cell chemoattractants and enhances cancer cell invasion of vascular basement membranes in vitro. Vascular endothelial cells are also susceptible to stimulation by systemic mediators including cytokines, thrombin, or endotoxin which induce a series of active responses in the vessel wall. These perturbed endothelial cells synthesize and express cell surface adhesion molecules which can interact with cancer cells. They also release chemoattractants which stimulate cancer cell motility. We postulate that such responses endow the vessel wall with the potential to act as a determinant of metastatic rate.

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Studies on the mechanisms of invasion in cancer. II. In vivo effects of a factor chemotactic for cancer cells

Cited by 59 publications

References 7 publications

A unique complement derived chemotactic factor for tumor cells.

A unique complement derived chemotactic factor for tumor cells.

Preferential splenic metastases in parabiotic animals

Cancer cell interactions with injured or activated endothelium

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