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| Content Provider | Springer Nature Link |
|---|---|
| Author | Pang, J. H. Coupland, L. A. Freeman, C. Chong, B. H. Parish, Christopher R. |
| Copyright Year | 2015 |
| Abstract | The promotion of tumour metastasis by platelets may occur through several mechanisms including the induction of a more metastatic phenotype in tumour cells and assisted extravasation of circulating tumour cells. Whilst the mechanisms underlying platelet-assisted extravasation have been extensively studied, much less attention has been paid to the mechanisms underlying platelet promotion of an aggressive phenotype within a tumour cell population. Herein, we demonstrate in vitro that MDA-MB-231 breast carcinoma cells incubated with washed thrombin-activated platelet membranes adopt a Matrigel-degrading phenotype in a dose- and contact time-dependent manner. The same phenotypic change was observed with three other human tumour cell lines of diverse anatomical origin. Moreover, tumour cell lines that had been cultured with washed thrombin-activated platelet membranes had a greater metastatic capacity when injected into mice. This in vivo effect was reliant upon a co-incubation period of >2 h implying a mechanism involving more than platelet membrane binding that occurred within 5 min. Upon further investigation it was found that simultaneous blocking of the platelet-membrane proteins P-selectin and GPIIb/IIIa prevented interactions between platelet membranes and MDA-MB-231 cells but also significantly reduced the ability of tumour cells to degrade Matrigel. These results confirm that platelets induce a more aggressive phenotype in tumour cells but also identify the platelet proteins involved in this effect. P-selectin and GPIIb/IIIa also play a role in assisting tumour cell extravasation and, thus, are ideal targets for the therapeutic intervention of both stages of platelet-assisted metastasis. |
| Starting Page | 495 |
| Ending Page | 505 |
| Page Count | 11 |
| File Format | |
| ISSN | 02620898 |
| Journal | Clinical & Experimental Metastasis |
| Volume Number | 32 |
| Issue Number | 5 |
| e-ISSN | 15737276 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2015-05-16 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Platelets Metastasis P-selectin GPIIb/IIIa Cancer Research Biomedicine general Oncology Hematology Surgical Oncology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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