Platelets guide the formation of early metastatic niches.
نویسندگان
چکیده
During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments ("niches") that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form "early metastatic niches." Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis.
منابع مشابه
Metastasis: new functional implications of platelets and megakaryocytes.
Platelets are essential components of hemostasis. Due to a plethora of factors released on activation, platelet functions are also connected to tumor growth, notably by acting on angiogenesis. It is now well recognized that major roles of platelets in the poor outcome of cancer patients occurs during hematogenous dissemination of cancer cells. In this review, we describe recent insights into th...
متن کاملThe mechanisms how heparin affects the tumor cell induced VEGF and chemokine release from platelets to attenuate the early metastatic niche formation
Metastasis is responsible for the majority of cancer associated fatalities. Tumor cells leaving the primary tumor and entering the blood flow immediately interact with platelets. Activated platelets contribute in different ways to cancer cell survival and proliferation, e.g. in formation of the early metastatic niche by release of different growth factors and chemokines. Here we show that a dir...
متن کاملMicroparticle Formation and Platelet Shrinkage in Type-I Glanzmman Thrombasthenia Platelets
Background: Activated normal platelets undergo many biochemical and morphological changes, some of which are apoptotic. Platelet derived microparticles and shrinked platelets as hallmark of platelet activation and apoptosis disperse surfaces containing procoagulant activity around injured vessels and tissues. This study was conducted to determine microparticles formation and platelet shrinkage ...
متن کاملHypoxia-driven immunosuppression contributes to the pre-metastatic niche
Primary tumor cells create favorable microenvironments in secondary organs, termed pre-metastatic niches, that promote the formation of metastases. Using immune competent syngenic breast cancer mouse models, we have recently demonstrated that factors secreted by hypoxic tumor cells condition pre-metastatic niches by recruiting CD11b+/Ly6Cmed/Ly6G+ myeloid cells and suppressing natural killer ce...
متن کاملپیشرفت هایی جدید در زمینه شناخت پلاکتها
Platelets as cellular elements are the constituants of blood tissue and their main function is to participate in hemostatic processes. The glycocalyx which intimately surrounds the platelets contains a number of glycoproteins which are responsible for blood group specificity (ABO), tissue compatibility (human leukocyte antigen = HLA) , and platelet antigenicity. Platelets contain granules which...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 111 30 شماره
صفحات -
تاریخ انتشار 2014