کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3026930 1182933 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Activated tumor cell integrin αvβ3 cooperates with platelets to promote extravasation and metastasis from the blood stream
چکیده انگلیسی


• Tumor cell subpopulations expressing high affinity integrin avb3 succeed in metastasis from the blood stream
• High affinity tumor cell integrin avb3 can support colonization of all major target organs during metastasis
• The mechanism depends on tumor cell-platelet interaction and platelet releasate supported tumor cell extravasation

ABSTRACTMetastasis 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Thrombosis Research - Volume 140, Supplement 1, April 2016, Pages S27–S36
نویسندگان
, , , , , , , , , , , , ,