L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma
Abstract The survival of tumor cells in the bloodstream, and vasculature adhesion at metastatic sites are crucial for tumor metastasis. Perivascular invasion aids tumor cell self-renewal, survival, and formation of metastases by facilitating readily available oxygen, nutrients, and endothelial-deriv...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-04-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01410-4 |
| _version_ | 1797850152468217856 |
|---|---|
| author | Zonglong Wu Yaqian Wu Zhuo Liu Yimeng Song Liyuan Ge Tan Du Yunchong Liu Li Liu Cheng Liu Lulin Ma |
| author_facet | Zonglong Wu Yaqian Wu Zhuo Liu Yimeng Song Liyuan Ge Tan Du Yunchong Liu Li Liu Cheng Liu Lulin Ma |
| author_sort | Zonglong Wu |
| collection | DOAJ |
| description | Abstract The survival of tumor cells in the bloodstream, and vasculature adhesion at metastatic sites are crucial for tumor metastasis. Perivascular invasion aids tumor cell self-renewal, survival, and formation of metastases by facilitating readily available oxygen, nutrients, and endothelial-derived paracrine factors. Renal cell carcinoma (RCC) is among the most prevalent tumors of the urinary system, and the formation of venous tumor thrombus (VTT) is a characteristic feature of RCC. We observed high expression of L1CAM in the VTT with vessel wall invasion. L1CAM promotes the adhesion, migration, and invasion ability of RCC and enhances metastasis by interacting with ITGA5, which elicits activation of signaling downstream of integrin α5β1. L1CAM promotes ADAM17 transcription to facilitate transmembrane ectodomain cleavage and release of soluble L1CAM. In response to soluble L1CAM, vascular endothelial cells release several cytokines and chemokines. Endothelial-derived CXCL5 and its receptor CXCR2 promote the migration and intravasation of RCC toward endothelial cells suggesting that crosstalk between endothelial cells and tumor cells has a direct guiding role in driving the metastatic spread of RCC. LICAM plays a crucial role in the invasive ability of RCC, and regulation of L1CAM expression may contribute therapeutically to preventing RCC progression. |
| first_indexed | 2024-04-09T18:56:51Z |
| format | Article |
| id | doaj.art-31293db6787946f7858c606e99451792 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-09T18:56:51Z |
| publishDate | 2023-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-31293db6787946f7858c606e994517922023-04-09T11:08:07ZengNature Publishing GroupCell Death Discovery2058-77162023-04-019111410.1038/s41420-023-01410-4L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinomaZonglong Wu0Yaqian Wu1Zhuo Liu2Yimeng Song3Liyuan Ge4Tan Du5Yunchong Liu6Li Liu7Cheng Liu8Lulin Ma9Department of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalSchool of Nursing, Beijing University of Chinese MedicineDepartment of Urology, Peking University Third HospitalDepartment of Urology, Peking University Third HospitalAbstract The survival of tumor cells in the bloodstream, and vasculature adhesion at metastatic sites are crucial for tumor metastasis. Perivascular invasion aids tumor cell self-renewal, survival, and formation of metastases by facilitating readily available oxygen, nutrients, and endothelial-derived paracrine factors. Renal cell carcinoma (RCC) is among the most prevalent tumors of the urinary system, and the formation of venous tumor thrombus (VTT) is a characteristic feature of RCC. We observed high expression of L1CAM in the VTT with vessel wall invasion. L1CAM promotes the adhesion, migration, and invasion ability of RCC and enhances metastasis by interacting with ITGA5, which elicits activation of signaling downstream of integrin α5β1. L1CAM promotes ADAM17 transcription to facilitate transmembrane ectodomain cleavage and release of soluble L1CAM. In response to soluble L1CAM, vascular endothelial cells release several cytokines and chemokines. Endothelial-derived CXCL5 and its receptor CXCR2 promote the migration and intravasation of RCC toward endothelial cells suggesting that crosstalk between endothelial cells and tumor cells has a direct guiding role in driving the metastatic spread of RCC. LICAM plays a crucial role in the invasive ability of RCC, and regulation of L1CAM expression may contribute therapeutically to preventing RCC progression.https://doi.org/10.1038/s41420-023-01410-4 |
| spellingShingle | Zonglong Wu Yaqian Wu Zhuo Liu Yimeng Song Liyuan Ge Tan Du Yunchong Liu Li Liu Cheng Liu Lulin Ma L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma Cell Death Discovery |
| title | L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma |
| title_full | L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma |
| title_fullStr | L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma |
| title_full_unstemmed | L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma |
| title_short | L1CAM deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma |
| title_sort | l1cam deployed perivascular tumor niche promotes vessel wall invasion of tumor thrombus and metastasis of renal cell carcinoma |
| url | https://doi.org/10.1038/s41420-023-01410-4 |
| work_keys_str_mv | AT zonglongwu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT yaqianwu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT zhuoliu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT yimengsong l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT liyuange l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT tandu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT yunchongliu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT liliu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT chengliu l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma AT lulinma l1camdeployedperivasculartumornichepromotesvesselwallinvasionoftumorthrombusandmetastasisofrenalcellcarcinoma |