Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream

Weber, Martin R; Zuka, Masahiko; Lorger, Mihaela; Tschan, Mario; Torbett, Bruce E; Zijlstra, Andries; Quigley, James P; Staflin, Karin; Eliceiri, Brian P; Krueger, Joseph S; Marchese, Patrizia; Ruggeri, Zaverio M; Felding, Brunhilde H (2016). Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream. Thrombosis research, 140(Suppl1), S27-36. Elsevier 10.1016/S0049-3848(16)30095-0

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Metastasis is the main cause of death in cancer patients, and understanding mechanisms that control tumor cell dissemination may lead to improved therapy. Tumor cell adhesion receptors contribute to cancer spreading. We noted earlier that tumor cells can expressing the adhesion receptor integrin αvβ3 in distinct states of activation, and found that cells which metastasize from the blood stream express it in a constitutively high affinity form. Here, we analyzed steps of the metastatic cascade in vivo and asked, when and how the affinity state of integrin αvβ3 confers a critical advantage to cancer spreading. Following tumor cells by real time PCR, non-invasive bioluminescence imaging, intravital microscopy and histology allowed us to identify tumor cell extravasation from the blood stream as a rate-limiting step supported by high affinity αvβ3. Successful transendothelial migration depended on cooperation between tumor cells and platelets involving the high affinity tumor cell integrin and release of platelet granules. Thus, this study identifies the high affinity conformer of integrin αvβ3 and its interaction with platelets as critical for early steps during hematogenous metastasis and target for prevention of metastatic disease.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

UniBE Contributor:

Tschan, Mario

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0049-3848

Publisher:

Elsevier

Language:

English

Submitter:

Mario Tschan

Date Deposited:

18 Jan 2017 12:48

Last Modified:

11 Sep 2017 16:07

Publisher DOI:

10.1016/S0049-3848(16)30095-0

PubMed ID:

27067975

Uncontrolled Keywords:

Blood stream; Extravasation; Integrin activation; Metastasis; Platelets

BORIS DOI:

10.7892/boris.92550

URI:

https://boris.unibe.ch/id/eprint/92550

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