Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts
Abstract Background Peritoneal metastasis (PM) is one of the most common causes of noncurative surgery and the most frequent recurrence pattern in gastric cancer (GC). During the process of PM, GC cells detached from primary tumor interact with human peritoneal mesothelial cells (HPMC) overlapped wi...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-01-01
|
| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.1647 |
| _version_ | 1811169282071986176 |
|---|---|
| author | Toshihide Hamabe‐Horiike Shin‐ichi Harada Kyoko Yoshida Jun Kinoshita Takahisa Yamaguchi Sachio Fushida |
| author_facet | Toshihide Hamabe‐Horiike Shin‐ichi Harada Kyoko Yoshida Jun Kinoshita Takahisa Yamaguchi Sachio Fushida |
| author_sort | Toshihide Hamabe‐Horiike |
| collection | DOAJ |
| description | Abstract Background Peritoneal metastasis (PM) is one of the most common causes of noncurative surgery and the most frequent recurrence pattern in gastric cancer (GC). During the process of PM, GC cells detached from primary tumor interact with human peritoneal mesothelial cells (HPMC) overlapped with adipose tissues such as the omentum or mesentery. Although the interaction with HPMC promotes the malignancy of GC, the role of adipose tissues remains unclear. Aims We aimed to clarify how adipose tissue are affected by adjacent primary tumors during the expression of adipokines and to elucidate whether GC cells transform adipocytes into CAFs in vitro. In addition, we investigated whether GC cells are affected by adipocytes in their ability to infiltrate. Methods We investigated the phenotypic conversion of adipocytes during the malignant process of GC cells in vivo and in vitro. We evaluated the expression levels of adiponectin in the omental adipose tissue of gastric cancer patients by western blotting. Following adipocytes/gastric cancer cells coculture, adipocyte markers, adiponectin receptors, and inflammatory cytokine markers were detected by real‐time PCR and/or western blotting in the single‐cultured and co‐cultured adipocytes; cancer‐associated fibroblast (CAF) markers were detected by immunofluorescence and western blotting in the single‐cultured and co‐cultured adipocytes; invasion assays were performed in single cultured and co‐cultured MKN45 and OCUM. Results In omental adipose tissues that are situated close to the primary tumors, the expression of adiponectin tended to decrease in patients with subserosal or serosal invasion. By co‐culturing with GC cells, adipocytes were dedifferentiated and the expression levels of CAF marker FSP1 and inflammatory cytokines, PAI‐1 and IL‐6, significantly increased (p < 0.05). Furthermore, GC cells co‐cultured with adipocytes showed enhanced invasion ability. Conclusion Our findings suggest that the phenotypic conversion of adipocytes may promote the malignancy of GC in the construction of the cancer microenvironment of PM. |
| first_indexed | 2024-04-10T16:39:45Z |
| format | Article |
| id | doaj.art-31dd3a024fc44e04a08512b85d5bcf68 |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-04-10T16:39:45Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-31dd3a024fc44e04a08512b85d5bcf682023-02-08T07:31:29ZengWileyCancer Reports2573-83482023-01-0161n/an/a10.1002/cnr2.1647Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblastsToshihide Hamabe‐Horiike0Shin‐ichi Harada1Kyoko Yoshida2Jun Kinoshita3Takahisa Yamaguchi4Sachio Fushida5Center for Biomedical Research and Education, School of Medicine Kanazawa University Kanazawa JapanCenter for Biomedical Research and Education, School of Medicine Kanazawa University Kanazawa JapanDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science Kanazawa University Kanazawa JapanDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science Kanazawa University Kanazawa JapanDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science Kanazawa University Kanazawa JapanDepartment of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science Kanazawa University Kanazawa JapanAbstract Background Peritoneal metastasis (PM) is one of the most common causes of noncurative surgery and the most frequent recurrence pattern in gastric cancer (GC). During the process of PM, GC cells detached from primary tumor interact with human peritoneal mesothelial cells (HPMC) overlapped with adipose tissues such as the omentum or mesentery. Although the interaction with HPMC promotes the malignancy of GC, the role of adipose tissues remains unclear. Aims We aimed to clarify how adipose tissue are affected by adjacent primary tumors during the expression of adipokines and to elucidate whether GC cells transform adipocytes into CAFs in vitro. In addition, we investigated whether GC cells are affected by adipocytes in their ability to infiltrate. Methods We investigated the phenotypic conversion of adipocytes during the malignant process of GC cells in vivo and in vitro. We evaluated the expression levels of adiponectin in the omental adipose tissue of gastric cancer patients by western blotting. Following adipocytes/gastric cancer cells coculture, adipocyte markers, adiponectin receptors, and inflammatory cytokine markers were detected by real‐time PCR and/or western blotting in the single‐cultured and co‐cultured adipocytes; cancer‐associated fibroblast (CAF) markers were detected by immunofluorescence and western blotting in the single‐cultured and co‐cultured adipocytes; invasion assays were performed in single cultured and co‐cultured MKN45 and OCUM. Results In omental adipose tissues that are situated close to the primary tumors, the expression of adiponectin tended to decrease in patients with subserosal or serosal invasion. By co‐culturing with GC cells, adipocytes were dedifferentiated and the expression levels of CAF marker FSP1 and inflammatory cytokines, PAI‐1 and IL‐6, significantly increased (p < 0.05). Furthermore, GC cells co‐cultured with adipocytes showed enhanced invasion ability. Conclusion Our findings suggest that the phenotypic conversion of adipocytes may promote the malignancy of GC in the construction of the cancer microenvironment of PM.https://doi.org/10.1002/cnr2.1647adipocytescancer‐associated fibroblastsgastric cancerperitoneal metastasis |
| spellingShingle | Toshihide Hamabe‐Horiike Shin‐ichi Harada Kyoko Yoshida Jun Kinoshita Takahisa Yamaguchi Sachio Fushida Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts Cancer Reports adipocytes cancer‐associated fibroblasts gastric cancer peritoneal metastasis |
| title | Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts |
| title_full | Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts |
| title_fullStr | Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts |
| title_full_unstemmed | Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts |
| title_short | Adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts |
| title_sort | adipocytes contribute to tumor progression and invasion of peritoneal metastasis by interacting with gastric cancer cells as cancer associated fibroblasts |
| topic | adipocytes cancer‐associated fibroblasts gastric cancer peritoneal metastasis |
| url | https://doi.org/10.1002/cnr2.1647 |
| work_keys_str_mv | AT toshihidehamabehoriike adipocytescontributetotumorprogressionandinvasionofperitonealmetastasisbyinteractingwithgastriccancercellsascancerassociatedfibroblasts AT shinichiharada adipocytescontributetotumorprogressionandinvasionofperitonealmetastasisbyinteractingwithgastriccancercellsascancerassociatedfibroblasts AT kyokoyoshida adipocytescontributetotumorprogressionandinvasionofperitonealmetastasisbyinteractingwithgastriccancercellsascancerassociatedfibroblasts AT junkinoshita adipocytescontributetotumorprogressionandinvasionofperitonealmetastasisbyinteractingwithgastriccancercellsascancerassociatedfibroblasts AT takahisayamaguchi adipocytescontributetotumorprogressionandinvasionofperitonealmetastasisbyinteractingwithgastriccancercellsascancerassociatedfibroblasts AT sachiofushida adipocytescontributetotumorprogressionandinvasionofperitonealmetastasisbyinteractingwithgastriccancercellsascancerassociatedfibroblasts |