Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches
A special microenvironment called the “pre-metastatic niche” is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches b...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Heliyon |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024051326 |
| _version_ | 1797221772197625856 |
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| author | Rui Qu Wenxuan Du Shuyao Li Wei Li Guangfei Wei Zhoujiang Chen Huile Gao Sanjun Shi Liang Zou Hanmei Li |
| author_facet | Rui Qu Wenxuan Du Shuyao Li Wei Li Guangfei Wei Zhoujiang Chen Huile Gao Sanjun Shi Liang Zou Hanmei Li |
| author_sort | Rui Qu |
| collection | DOAJ |
| description | A special microenvironment called the “pre-metastatic niche” is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation. However, when human umbilical vein endothelial cultures were treated in vitro with these secreted pro-metastatic factors, no significant destruction of the glycocalyx was observed, implying that this destruction requires a complex in vivo microenvironment. The tissue section analysis revealed that secreted pro-metastatic factors could clearly upregulate macrophage-related molecules such as CD11b and tumor necrosis factor-α (TNF-α) in the heart, liver, spleen, lung, and kidney, which is associated with the upregulation and activation of heparanase. In addition, macrophage depletion significantly attenuated the degradation of the vascular endothelial glycocalyx induced by secreted pro-metastatic factors. This indicates that the secreted pro-metastatic factors that destroy the vascular endothelial glycocalyx rely primarily on macrophages. Our findings suggest that the formation of pre-metastatic niches involves degradation of the vascular endothelial glycocalyx, which may hence be a useful target for developing therapies to inhibit cancer metastasis. |
| first_indexed | 2024-04-24T13:10:45Z |
| format | Article |
| id | doaj.art-83f814caf1d24b619cae010065dc2f78 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:10:45Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-83f814caf1d24b619cae010065dc2f782024-04-05T04:41:22ZengElsevierHeliyon2405-84402024-04-01107e29101Destruction of vascular endothelial glycocalyx during formation of pre-metastatic nichesRui Qu0Wenxuan Du1Shuyao Li2Wei Li3Guangfei Wei4Zhoujiang Chen5Huile Gao6Sanjun Shi7Liang Zou8Hanmei Li9Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, ChinaSichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, ChinaSchool of Food and Biological Engineering, Chengdu University, Chengdu, 610106, ChinaClinical Medical Research Center, Zhenjiang Hospital of Integrated Traditional Chinese and Western Medicine, Zhenjiang, 212004, ChinaSchool of Food and Biological Engineering, Chengdu University, Chengdu, 610106, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research, Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, ChinaSchool of Food and Biological Engineering, Chengdu University, Chengdu, 610106, ChinaSchool of Food and Biological Engineering, Chengdu University, Chengdu, 610106, China; Corresponding author.A special microenvironment called the “pre-metastatic niche” is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation. However, when human umbilical vein endothelial cultures were treated in vitro with these secreted pro-metastatic factors, no significant destruction of the glycocalyx was observed, implying that this destruction requires a complex in vivo microenvironment. The tissue section analysis revealed that secreted pro-metastatic factors could clearly upregulate macrophage-related molecules such as CD11b and tumor necrosis factor-α (TNF-α) in the heart, liver, spleen, lung, and kidney, which is associated with the upregulation and activation of heparanase. In addition, macrophage depletion significantly attenuated the degradation of the vascular endothelial glycocalyx induced by secreted pro-metastatic factors. This indicates that the secreted pro-metastatic factors that destroy the vascular endothelial glycocalyx rely primarily on macrophages. Our findings suggest that the formation of pre-metastatic niches involves degradation of the vascular endothelial glycocalyx, which may hence be a useful target for developing therapies to inhibit cancer metastasis.http://www.sciencedirect.com/science/article/pii/S2405844024051326 |
| spellingShingle | Rui Qu Wenxuan Du Shuyao Li Wei Li Guangfei Wei Zhoujiang Chen Huile Gao Sanjun Shi Liang Zou Hanmei Li Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches Heliyon |
| title | Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches |
| title_full | Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches |
| title_fullStr | Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches |
| title_full_unstemmed | Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches |
| title_short | Destruction of vascular endothelial glycocalyx during formation of pre-metastatic niches |
| title_sort | destruction of vascular endothelial glycocalyx during formation of pre metastatic niches |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024051326 |
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