Tumor‐cell‐platelet aggregation does not correlate with metastatic potential of rat 13762NF mammary adenocarcinoma tumor cell clones

Abstract

The ability of tumor cells to induce platelet aggregation has been correlated with their capacities to colonize the lungs of experimental animals. We tested this hypothesis by studying the ability of cloned, low-passage metastatic tumor cell lines derived from rat 13762NF mammary adenocarcinoma to aggregate rat platelets in vitro and in vivo, and we then compared this activity to metastatic potential by determining the incidence of lung metastasis after subcutaneous or intravenous inoculation of the tumor cell clones into syngeneic rats. Our results failed to show a correlation between in vitro platelet-aggregating activity and metastatic potential. In this system we could not detect platelet-aggregation activity with the most metastatic tumor clone, while least metastatic clone clearly possessed high platelet-aggregating activity. In addition, by measuring changes in blood platelet and fibrinogen concentrations at various intervals following intravenous injection of tumor cell clones, we were able to confirm in vivo the observed in vitro differences in their platelet-aggregating activities. Thus, platelet aggregating activity is heterogeneously expressed among 13762NF cell clones and appears unrelated to spontaneous or experimental metastasis in this tumor system.

Platelets and cancer metastasis: A causal relationship?

“…For example, we reexamined the lack of correlation between homologous platelet aggregation and lung colonization by subclones MTC and MTLn 3 of the rat 13762NF mammary adenocarcinoma. In agreement with the published report [68], we observed that low metastatic MTC cells induced aggregation of rat platelets while high metastatic MTLn 3 cells did not induce platelet aggregation when we tested cells derived from culture ( Fig. 1).…”

“…However, it is worthwhile to consider that rarely does a concept or hypothesis find a universal application, especially when dynamic cell-cell interactions are considered. Therefore it is not unexpected that some experimental results present in the literature are in disagreement, i.e., no definitive correlation can be demonstrated between TCIPA and metastatic potential [68,69], with the conclusion we present in this review. These conflicting results should, in principle, find easy reconciliation from the fact that tumor cells are highly heterogeneous and this heterogeneity can be further impinged upon by a large array of external and internal factors, including various experimental manipulations.…”

Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites

“…Many tumor systems stimulate the formation of surrounding fibrin deposits around arrested malignant cells in the microcirculation, and their thromboplastic and platelet-aggregating activities are related to their blood-borne implantation properties [131][132][133][134][135][136]. Not all highly metastatic cells, however, have high platelet [137,138] and thromboplastic activities [139].…”

The stable prostacyclin analogue Cicaprost inhibits metastasis to lungs and lymph nodes in the 13762NF MTLn3 rat mammary carcinoma

“…In this study we used the highly metastatic cell clone MTLn3 isolated from the 13762NF tumour system by Neri et al [11]. This cell clone injected into the blood circulation did not alter platelet count, indicating failure to induce platelet aggregation [24]. Nicolson et al [25,26] have demonstrated that the MTLn3 cells adhere to and invade lung tissue at significantly higher rates than poorly metastatic cell clones isolated from the 13762NF tumour.…”