Plasma thrombospondin levels in patients with gynecologic malignancies

Abstract

Background. Thrombospondin is a high molecular weight glycoprotein, originally described as a secretion product of platelets, that functions as an adhesive protein in cell‐cell and cell‐substratum interactions. It promotes metastases in the murine model. Plasma thrombospondin has been shown to be elevated in patients with disseminated breast, lung, and gastrointestinal malignancies. Methods. Blood samples were collected by venipunc‐ture into cubes containing ethylenediamine tetraacetic acid as anticoagulant. They were placed on ice immediately and centrifuged under refrigerated conditions. Plasma was removed and frozen until thrombospondin was quantitated by a competitive enzyme‐linked immu‐nosorbent assay. Wilcoxon's two‐sample rank‐sum test was used to evaluate differences between the patient and control groups. Results. The median plasma thrombospondin level was significantly higher in the patient group compared with the control group, and it was directly correlated with stage of disease. There was no correlation between platelet count and thrombospondin level. Conclusions. Tumor‐synthesized thrombospondin could explain the elevated levels in the patent group and also the observation of the correlation between the thrombospondin level and tumor burden. Its function as an adhesive protein may allow it to act as the mediator of metastases. thrombospondin may promote or mediate the metastatic process through its function in cell adhesion. Cancer 1994; 73:2853–8.

Thrombospondin-1, an inhibitor of angiogenesis, is regulated by progesterone in the human endometrium.

“…TSP was detected in the initial "aqueous phase" of milk secretion and its levels subsequently fell during the transition to mature milk (38). More recently, changes in plasma TSP1 have also been identified in patients with gynecological malignancies (41).…”

The role of thrombospondin-1 in human disease1

“…TSP-1 levels were significantly increased in patients with gastrointestinal, breast, and lung cancer when compared to control patients who were medically ill or normal. Additionally, patients with advancedstage gynecologic and colon cancer had significantly higher TSP-1 levels when compared with early stage patients [33,34]. As well, more aggressive signs, such as venous invasion by tumors in patients with colorectal carcinoma, had higher TSP-1 levels than those without venous invasion [34].…”

Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis

“…Under normal physiologic conditions, TSP-1 plasma levels are very low, whereas in cancer patients and certain mouse models, its levels have been shown to increase. [47][48][49][50][51] One explanation for the observed (B) Endothelial cell migration was measured in the absence of VEGF (Ctrl.) or in response to VEGF (5 ng/mL) in the presence of thrombin, or thrombin-treated platelet lysates from wild-type mice or tumor-bearing (500 mm 3 ) wild-type mice (P ϭ .001).…”