Characterization of tumor-induced platelet aggregation: The role of immunorelated GPIb and expression by MCF-7 breast cancer cells

Oleksowicz, Leslie; Mrowiec, Zbigniew; Schwartz, Edward L.; Khorshidi, Manoochehr; Dutcher, Janice P.; Puszkin, Elena

doi:10.1016/0049-3848(95)00113-6

Cited by 69 publications

(56 citation statements)

References 26 publications

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“…The finding that aIIbb3 protein is expressed in MCF-7 cells is interesting because of the relatively low expression of b3 mRNA. Our finding that aIIbb3 protein is functionally expressed in these cells, in conjunction with a report documenting the expression of a GPIIb/IIIa-like protein in these cells (Oleksowicz et al, 1995), suggests that the level of aIIbb3 mRNA is not the sole determinant of protein expression. Similarly, even though SKHEP-1 cells express aIIb/b3 mRNAs, these cells express the protein intracellularly, but not on the cell surface, which is indicative of a post-translational mechanism of aIIbb3 expression.…”

Section: Discussionsupporting

confidence: 64%

“…Although these results do not represent all tumor cells, they suggest that aIIb and b3 mRNAs are translated into corresponding proteins in several non-megakaryocytic lineage tumor cells. Regarding the function of aIIbb3 in tumor cells, several reports indicate that aIIbb3 integrin is involved in tumor-cell-induced platelet aggregation, tumor-cell adhesion to endothelial cells and subendothelial matrix and invasion of tumor cells through a reconstituted basement membrane (Chiang et al, 1994;Oleksowicz et al, 1995;Timar et al, 1996;Trikha et al, 1996). These cell-cell and cell-matrix interactions are crucial during the hematogenous phase of tumor-cell metastasis (Tang and Honn, 1994), and are supported by the report that increased aIIbb3 expression in subpopulations of B16a cells correlates positively with their lung colonization ability (Chang et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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Ectopic expression of platelet integrin αIIbβ3 in tumor cells from various species and histological origin

et al. 1997

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The integrin aIIbb3 is a membrane receptor which was considered to be expressed only in cells of megakaryocytic lineage. We have shown that aIIbb3 is expressed in mouse melanoma B16a cells, and in human prostate adenocarcinoma cells. The purpose of this study was to determine whether the megakaryocytic product aIIbb3 was functionally expressed in other non-megakaryocyte lineage tumor cells. By using the reverse transcription polymerase chain reaction (RT-PCR), we have obtained data demonstrating that aIIbb3 is expressed in a variety of tumor cell lines (17) derived from different species (human, rat and mouse) and of different histological origins (skin, blood, lung, liver, kidney, cervix, colon, bladder, breast and prostate). Immunostaining of tumor cells with a monoclonal antibody (MAb) to aIIbb3 demonstrates that aIIbb3 protein is also expressed in tumor cells. A protein kinase C activator PMA stimulates adhesion of tumor cells to fibronectin and fibrinogen, and this stimulated adhesion is blocked by a function-blocking MAb directed to aIIbb3. Our results indicate that the megakaryocytic gene product aIIbb3 integrin is widely expressed among tumor cells of non-megakaryocytic lineage, suggesting that ectopic expression of this integrin may play an important role in tumor progression. Int.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Ectopic expression of platelet integrin αIIbβ3 in tumor cells from various species and histological origin

et al. 1997

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“…Several studies showed that circulating tumor cells could cause an activation and aggregation of platelets [3,33,34]. Our data also suggest that platelets play a direct role during development of micro-metastases in the MT3 model, because the blood clotting time was found to be significantly longer and platelet aggregation was significantly impaired ex vivo after MT3 breast cancer cell inoculation into nude mice.…”

Section: Discussionsupporting

confidence: 66%

Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation

Wenzel

Zeisig

Haider³

et al. 2009

Breast Cancer Res Treat

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The process of metastasis formation in cancer is not completely understood and is the main reason cancer therapies fail.Previously, we showed that dual liposomes simultaneously containing the haemostatic inhibitor, dipyridamole and the anticancer drug, perifosine potently inhibited metastasis, causing a 90% reduction in the number of lung metastases in a murine experimental metastasis model. To gain deeper insight into the mechanisms leading to the inhibition of metastasis by these dual liposomes, in the present study, the development of metastases by MT3 breast cancer cells in a mouse xenograft model was analyzed in more detail with regard to tumor cell settlement and metastatic growth.We found that the development of lung metastases by MT3 tumor cells is essentially dependent on the formation of fibrin clots as a precondition for the pulmonary arrest of tumor cells and the subsequent intravascular expansion of micro-metastases before their invasion into the surrounding tissue.3

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“…The expression of Gp1b␣ by 32D myeloid cells is perhaps not surprising, given that they share a common lineage with bone marrow megakaryocytes (27,29). GpIb␣ has also been detected in normal endothelial cells, dermal dendrocytes, MCF7 breast cancer cells, and primary breast cancers but not in normal mammary tissue (33)(34)(35)(36). To explore the possibility that ploidy might normally be under the control of Gp1b␣ in other cell types, we examined a variety of tissues and cell lines for the expression of Gp1b␣ mRNA and protein.…”

Section: Gp1b␣ Overexpression Is Sufficient For the Induction Of Tetrmentioning

confidence: 99%

c-Myc-mediated genomic instability proceeds via a megakaryocytic endomitosis pathway involving Gp1bα

Prochownik

2007

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

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Genomic instability (GI) is essential for the initiation and evolution of many cancers and often precedes frank neoplastic conversion. Although GI can occur at several levels, the most conspicuous examples involve gains or losses of entire chromosomes (aneuploidy), the antecedent of which may be whole genome duplication (tetraploidy). Through largely undefined mechanisms, the c-Myc oncoprotein and its downstream target, MTMC1, promote tetraploidy and other forms of GI. In myeloid cells, c-Myc and MTMC1 also regulate a common, small subset of c-Myc target genes including GP1B α, which encodes a subunit of the von Willebrand's factor receptor complex that mediates platelet adhesion and aggregation. Gp1bα also participates in megakaryocyte endomitosis, a form of controlled and precise whole-genome amplification. In this article, we show that both c-Myc and MTMC1 strongly up-regulate Gp1bα concurrent with their promotion of tetraploidy. shRNA-mediated inhibition of Gp1bα prevents tetraploidy by both c-Myc and MTMC1, whereas Gp1bα overexpression alone is sufficient to induce tetraploidy in established and primary cells. Once acquired, tetraploidy persists in most cases examined. Our results indicate that chromosome-level GI, induced by c-Myc overexpression, proceeds by means of the sequential up-regulation of MTMC1 and Gp1bα and further suggest that the pathways leading to megakaryocytic endomitosis and c-Myc-induced tetraploidy are mechanistically linked by their reliance on Gp1bα.

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Characterization of tumor-induced platelet aggregation: The role of immunorelated GPIb and expression by MCF-7 breast cancer cells

Cited by 69 publications

References 26 publications

Ectopic expression of platelet integrin αIIbβ3 in tumor cells from various species and histological origin

Ectopic expression of platelet integrin αIIbβ3 in tumor cells from various species and histological origin

Inhibition of pulmonary metastasis in a human MT3 breast cancer xenograft model by dual liposomes preventing intravasal fibrin clot formation

c-Myc-mediated genomic instability proceeds via a megakaryocytic endomitosis pathway involving Gp1bα

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