Significance of platelets in an antimetastatic activity of bacterial lipopolysaccharide

Abstract

Recently we reported an antimetastatic activity of bacterial lipopolysaccharide (LPS) on a NK-cell-resistant murine fibrosarcoma (NFSa). Here we investigate and report the mechanistic significance of platelets in this activity. The number of circulating platelets was reduced to 63% of the control 3 days after an i.v. injection of 1.0 micrograms LPS, and then recovered to the level of control at day 10. Aggregation efficiency of platelets was impaired by LPS. The number of metastatic lung colonies after an i.v. injection of tumor cells was maximally reduced to 2.2% of the control at day 3 and increased in proportion to the recovery of platelet number. Neuraminidase (Ndase), which caused a non-immunological thrombocytopenia, also inhibited lung metastasis when injected prior to an i.v. tumor cell challenge. LPS and Ndase showed an identical pattern against five other syngeneic tumors; these agents inhibited lung metastases of the FSa fibrosarcoma and the SCC VII squamous cell carcinoma but failed to inhibit those of the NR-S1 squamous cell carcinoma, the MMCa#4 mammary adenocarcinoma and the NR-PG parotid gland tumor. All the three cells which were not responsive to any agents possessed a high aggregating activity of platelets while the other three tumors responsive to both agents did not show a detectable level of this activity. Platelet transfusion failed to modify the antimetastatic activity of LPS. These results suggest that platelets play an important role in the antimetastatic activity of LPS, though whether the role is principal or assistant remains to be seen.

Tumor cell adhesion under hydrodynamic conditions of fluid flow

“…Although tumor cell adhesion can occur under static conditions without binding of platelets, under the influence of fluid flow these adhesive bonds were only established if platelets interacted with the melanoma cells (132). This is supported by in-vivo results indicating that a lack of platelets or their impaired function can reduce metastasis formation in a variety of cell systems (133). Under static conditions, the presence of platelets did not affect the adhesive properties of A549 lung carcinoma cells to EC or ECM components.…”

Role of β3 Integrins in Melanoma Cell Adhesion to Activated Platelets under Flow

“…A number of reports indicate that interference with platelet function in vivo reduced tumor metastasis in animal models. Moreover, reduction of platelet counts inhibited metastasis of a variety of tumor cells including melanomas, carcinomas, and sarcomas (11)(12)(13)(14). In these cases, metastasis was reduced regardless of the ability of the tumor cells to induce platelet aggregation in vitro (26 -28).…”

“…It has long been thought that platelets may assist hematogenous dissemination of metastasizing cells (8 -10). Perhaps the most convincing evidence is the inhibition of metastasis by experimental thrombocytopenia shown for a variety of tumors (11)(12)(13)(14). We therefore hypothesized that tumor cells may interact with platelets and thereby acquire specific mechanisms which mediate platelet anchorage under flow.…”

How platelet aggregation affects B16BL6 melanoma cell trafficking

“…In fact, tumor cell‐induced platelet aggregation‐inhibiting agents [10], peptides [11], or antibody [12, 13]have been known to suppress tumor metastasis. Similarly, lipopolysaccharide‐induced platelet starvation reduced the metastatic potential of murine fibrosarcoma [14]. Therefore, it is possible that platelet aggregation plays an important role in establishment of metastasis of some tumors, but not essential to some other tumors such as B16BL6.…”