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Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression
Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450461/ https://www.ncbi.nlm.nih.gov/pubmed/34552935 http://dx.doi.org/10.3389/fcell.2021.741820 |
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author | Davuluri, Goutham Venkata Naga Chen, Chien-Chin Chiu, Yen-Cheng Tsai, Hung-Wen Chiu, Hung-Chih Chen, Yuh-Ling Tsai, Pei-Jane Kuo, Wan-Ting Tsao, Nina Lin, Yee-Shin Chang, Chih-Peng |
author_facet | Davuluri, Goutham Venkata Naga Chen, Chien-Chin Chiu, Yen-Cheng Tsai, Hung-Wen Chiu, Hung-Chih Chen, Yuh-Ling Tsai, Pei-Jane Kuo, Wan-Ting Tsao, Nina Lin, Yee-Shin Chang, Chih-Peng |
author_sort | Davuluri, Goutham Venkata Naga |
collection | PubMed |
description | Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression. |
format | Online Article Text |
id | pubmed-8450461 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84504612021-09-21 Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression Davuluri, Goutham Venkata Naga Chen, Chien-Chin Chiu, Yen-Cheng Tsai, Hung-Wen Chiu, Hung-Chih Chen, Yuh-Ling Tsai, Pei-Jane Kuo, Wan-Ting Tsao, Nina Lin, Yee-Shin Chang, Chih-Peng Front Cell Dev Biol Cell and Developmental Biology Galectin-1 (Gal-1) is a secretory lectin with pro-tumor activities and is associated strongly with hepatocellular carcinoma (HCC) development. Although Gal-1 is a well-known soluble pro-tumor factor in the tumor microenvironment (TME), the secretion mode of Gal-1 is not clearly defined. On the other hand, in addition to cancer cells, Gal-1 is widely expressed in tumor stromal cells, including tumor-associated macrophages (TAMs). TAMs are a significant component of stromal cells in TME; however, their contributions in producing Gal-1 to TME are still not explored. Here we reveal that TAMs can actively secrete Gal-1 in response to stimuli of HCC cells. Gal-1 produced by TAMs leads to an increase of the systemic level of Gal-1 and HCC tumor growth in mice. Mechanistically, TLR2-dependent secretory autophagy is found to be responsible for Gal-1 secretion from TAMs. Gal-1 acts as a cargo of autophagosomes to fuse with multivesicular bodies via Rab11 and VAMP7-mediated vesicle trafficking before being secreted. This autophagy-regulated Gal-1 secretion in TAMs correlates to poor overall survival and progression-free survival rates of HCC patients. Our findings uncover the secretion mode of Gal-1 via secretory autophagy and highlight the pathological role of TAM-produced Gal-1 in HCC progression. Frontiers Media S.A. 2021-09-06 /pmc/articles/PMC8450461/ /pubmed/34552935 http://dx.doi.org/10.3389/fcell.2021.741820 Text en Copyright © 2021 Davuluri, Chen, Chiu, Tsai, Chiu, Chen, Tsai, Kuo, Tsao, Lin and Chang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Davuluri, Goutham Venkata Naga Chen, Chien-Chin Chiu, Yen-Cheng Tsai, Hung-Wen Chiu, Hung-Chih Chen, Yuh-Ling Tsai, Pei-Jane Kuo, Wan-Ting Tsao, Nina Lin, Yee-Shin Chang, Chih-Peng Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression |
title | Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression |
title_full | Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression |
title_fullStr | Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression |
title_full_unstemmed | Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression |
title_short | Autophagy Drives Galectin-1 Secretion From Tumor-Associated Macrophages Facilitating Hepatocellular Carcinoma Progression |
title_sort | autophagy drives galectin-1 secretion from tumor-associated macrophages facilitating hepatocellular carcinoma progression |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450461/ https://www.ncbi.nlm.nih.gov/pubmed/34552935 http://dx.doi.org/10.3389/fcell.2021.741820 |
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