Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis
ABSTRACT Metastasis is the main cause of cancer‐related deaths and the biggest challenge in improving cancer prognosis. Platelet–tumor cell aggregates are a prerequisite for hematogenous metastasis. However, the internal relation and molecular mechanism of platelets and their receptor glycoprotein (...
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2025-06-01
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| Online Access: | https://doi.org/10.1002/mco2.70217 |
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| author | Kangxi Zhou Qing Li Yue Xia Chenglin Sun Jing Wang Yueyue Sun Xinxin Ge Mengnan Yang Yu Li Sai Zhang Lili Zhao Chunliang Liu Khan Muhammad Shoaib Weiling Xiao Renping Hu Kesheng Dai Rong Yan |
| author_facet | Kangxi Zhou Qing Li Yue Xia Chenglin Sun Jing Wang Yueyue Sun Xinxin Ge Mengnan Yang Yu Li Sai Zhang Lili Zhao Chunliang Liu Khan Muhammad Shoaib Weiling Xiao Renping Hu Kesheng Dai Rong Yan |
| author_sort | Kangxi Zhou |
| collection | DOAJ |
| description | ABSTRACT Metastasis is the main cause of cancer‐related deaths and the biggest challenge in improving cancer prognosis. Platelet–tumor cell aggregates are a prerequisite for hematogenous metastasis. However, the internal relation and molecular mechanism of platelets and their receptor glycoprotein (GP) Ibα in platelet–tumor cell interaction and metastasis remain elusive. Here, we find that in the absence of the full‐length GPIbα or its cytoplasmic tail, platelets maintain a more resting state and exhibit reduced tumor cell‐induced platelet activation. The deficiency of the cytoplasmic tail of GPIbα inhibits tumor cell–platelet interaction, platelet‐induced tumor cell migration and invasion, and metastasis. Using a state‐of‐the‐art spinning disk intravital microscopy, we observe a rapid accumulation of platelets on tumor cells, forming numerous tumor cell–platelet aggregates in vivo. We also find that the cytoplasmic tail of GPIbα regulates the tumor cell‐induced platelet protein kinase C‐α (PKCα) activation, and both the pharmacological inhibition and genetic ablation of platelet PKCα attenuate tumor cell‐induced platelet activation, tumor cell–platelet interaction, tumor cell migration and invasion, and metastasis. Overall, our findings reveal for the first time that GPIbα promotes experimental metastasis through its cytoplasmic tail‐regulated platelet activation, and suggest a potential target to regulate tumor hematogenous metastasis. |
| format | Article |
| id | doaj-art-987b03fddee8496da5fc1ce550229fd0 |
| institution | DOAJ |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-987b03fddee8496da5fc1ce550229fd02025-08-20T02:56:34ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70217Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental MetastasisKangxi Zhou0Qing Li1Yue Xia2Chenglin Sun3Jing Wang4Yueyue Sun5Xinxin Ge6Mengnan Yang7Yu Li8Sai Zhang9Lili Zhao10Chunliang Liu11Khan Muhammad Shoaib12Weiling Xiao13Renping Hu14Kesheng Dai15Rong Yan16Jiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaJiangsu Institute of Hematology The First Affiliated Hospital of Soochow University, Cyrus Tang Medical Institute Suzhou Medical College, Soochow University, NHC Key Laboratory of Thrombosis and Hemostasis, National Clinical Research Center for Hematological Diseases Suzhou Jiangsu ChinaABSTRACT Metastasis is the main cause of cancer‐related deaths and the biggest challenge in improving cancer prognosis. Platelet–tumor cell aggregates are a prerequisite for hematogenous metastasis. However, the internal relation and molecular mechanism of platelets and their receptor glycoprotein (GP) Ibα in platelet–tumor cell interaction and metastasis remain elusive. Here, we find that in the absence of the full‐length GPIbα or its cytoplasmic tail, platelets maintain a more resting state and exhibit reduced tumor cell‐induced platelet activation. The deficiency of the cytoplasmic tail of GPIbα inhibits tumor cell–platelet interaction, platelet‐induced tumor cell migration and invasion, and metastasis. Using a state‐of‐the‐art spinning disk intravital microscopy, we observe a rapid accumulation of platelets on tumor cells, forming numerous tumor cell–platelet aggregates in vivo. We also find that the cytoplasmic tail of GPIbα regulates the tumor cell‐induced platelet protein kinase C‐α (PKCα) activation, and both the pharmacological inhibition and genetic ablation of platelet PKCα attenuate tumor cell‐induced platelet activation, tumor cell–platelet interaction, tumor cell migration and invasion, and metastasis. Overall, our findings reveal for the first time that GPIbα promotes experimental metastasis through its cytoplasmic tail‐regulated platelet activation, and suggest a potential target to regulate tumor hematogenous metastasis.https://doi.org/10.1002/mco2.70217glycoprotein Ibαmetastasisplatelet activationtumor cell–platelet interaction |
| spellingShingle | Kangxi Zhou Qing Li Yue Xia Chenglin Sun Jing Wang Yueyue Sun Xinxin Ge Mengnan Yang Yu Li Sai Zhang Lili Zhao Chunliang Liu Khan Muhammad Shoaib Weiling Xiao Renping Hu Kesheng Dai Rong Yan Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis MedComm glycoprotein Ibα metastasis platelet activation tumor cell–platelet interaction |
| title | Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis |
| title_full | Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis |
| title_fullStr | Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis |
| title_full_unstemmed | Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis |
| title_short | Glycoprotein Ibα‐Dependent Platelet Activation is Essential for Tumor Cell–Platelet Interaction and Experimental Metastasis |
| title_sort | glycoprotein ibα dependent platelet activation is essential for tumor cell platelet interaction and experimental metastasis |
| topic | glycoprotein Ibα metastasis platelet activation tumor cell–platelet interaction |
| url | https://doi.org/10.1002/mco2.70217 |
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