Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4
Calreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulator...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/4626813 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832563068298592256 |
|---|---|
| author | Hong-Min Wang Zhe Zhou Jie Miao Bo Zhu Xiao-Qiu Dai Qiao Zhong Fang-Yuan Gong Xiao-Ming Gao |
| author_facet | Hong-Min Wang Zhe Zhou Jie Miao Bo Zhu Xiao-Qiu Dai Qiao Zhong Fang-Yuan Gong Xiao-Ming Gao |
| author_sort | Hong-Min Wang |
| collection | DOAJ |
| description | Calreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulatory effects as well as immunoregulation effects on immune cells. Here, we constructed stable B16 melanoma cell lines expressing recombinant CRT/39-272 on the membrane (B16-tmCRT/39-272) to investigate the roles of cell surface CRT on tumor progression. We found that B16-tmCRT/39-272 cells subcutaneously inoculated into C57BL/6 mice exhibited stronger tumorigenicity than the B16-EGFP control cells. The tumor associated macrophages infiltrated in tumors were mainly M2 phenotype. Regulatory T cells (Tregs) were also expanded more in bearing mice. Consistent with the in vivo results, B16-tmCRT/39-272 promoted macrophage polarization toward F4/80+CD206+ M2 macrophages and promoted transforming growth factor beta (TGF-β) secretion in vitro, which could promote naïve CD4+T cell differentiation into Tregs. These results imply that the tmCRT/39-272 could accelerate tumor development by enhancing M2 macrophage polarization to induce TGF-β secretion, and then promoted Treg differentiation in the tumor microenvironment. Our data may provide useful clues for better understanding of the potentiating roles of CRT in tumorigenesis. |
| format | Article |
| id | doaj-art-0c364a4662684089a1ca7fcde25be9b8 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-0c364a4662684089a1ca7fcde25be9b82025-02-03T01:21:04ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/4626813Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4Hong-Min Wang0Zhe Zhou1Jie Miao2Bo Zhu3Xiao-Qiu Dai4Qiao Zhong5Fang-Yuan Gong6Xiao-Ming Gao7Institute of Biology and Medical SciencesInstitute of Biology and Medical SciencesInstitute of Biology and Medical SciencesInstitute of Biology and Medical SciencesInstitute of Biology and Medical SciencesDepartment of Laboratory MedicineInstitute of Biology and Medical SciencesInstitute of Biology and Medical SciencesCalreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulatory effects as well as immunoregulation effects on immune cells. Here, we constructed stable B16 melanoma cell lines expressing recombinant CRT/39-272 on the membrane (B16-tmCRT/39-272) to investigate the roles of cell surface CRT on tumor progression. We found that B16-tmCRT/39-272 cells subcutaneously inoculated into C57BL/6 mice exhibited stronger tumorigenicity than the B16-EGFP control cells. The tumor associated macrophages infiltrated in tumors were mainly M2 phenotype. Regulatory T cells (Tregs) were also expanded more in bearing mice. Consistent with the in vivo results, B16-tmCRT/39-272 promoted macrophage polarization toward F4/80+CD206+ M2 macrophages and promoted transforming growth factor beta (TGF-β) secretion in vitro, which could promote naïve CD4+T cell differentiation into Tregs. These results imply that the tmCRT/39-272 could accelerate tumor development by enhancing M2 macrophage polarization to induce TGF-β secretion, and then promoted Treg differentiation in the tumor microenvironment. Our data may provide useful clues for better understanding of the potentiating roles of CRT in tumorigenesis.http://dx.doi.org/10.1155/2022/4626813 |
| spellingShingle | Hong-Min Wang Zhe Zhou Jie Miao Bo Zhu Xiao-Qiu Dai Qiao Zhong Fang-Yuan Gong Xiao-Ming Gao Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4 Journal of Immunology Research |
| title | Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4 |
| title_full | Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4 |
| title_fullStr | Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4 |
| title_full_unstemmed | Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4 |
| title_short | Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4 |
| title_sort | membrane bound crt fragment accelerates tumor growth of melanoma b16 cell in vivo through promoting m2 polarization via tlr4 |
| url | http://dx.doi.org/10.1155/2022/4626813 |
| work_keys_str_mv | AT hongminwang membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT zhezhou membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT jiemiao membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT bozhu membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT xiaoqiudai membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT qiaozhong membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT fangyuangong membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 AT xiaominggao membraneboundcrtfragmentacceleratestumorgrowthofmelanomab16cellinvivothroughpromotingm2polarizationviatlr4 |