Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that typically features a dramatic desmoplastic reaction, especially fibroblasts. The roles of cancer-associated fibroblasts (CAFs) in PDAC have received more attention in recent years. As increasing evidence suggests the heterogenei...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.655152/full |
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| author | Xinglong Geng Xinglong Geng Xinglong Geng Hongze Chen Hongze Chen Liang Zhao Jisheng Hu Jisheng Hu Wenbo Yang Wenbo Yang Guanqun Li Guanqun Li Chundong Cheng Chundong Cheng Zhongjie Zhao Zhongjie Zhao Tao Zhang Tao Zhang Le Li Le Li Bei Sun Bei Sun |
| author_facet | Xinglong Geng Xinglong Geng Xinglong Geng Hongze Chen Hongze Chen Liang Zhao Jisheng Hu Jisheng Hu Wenbo Yang Wenbo Yang Guanqun Li Guanqun Li Chundong Cheng Chundong Cheng Zhongjie Zhao Zhongjie Zhao Tao Zhang Tao Zhang Le Li Le Li Bei Sun Bei Sun |
| author_sort | Xinglong Geng |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that typically features a dramatic desmoplastic reaction, especially fibroblasts. The roles of cancer-associated fibroblasts (CAFs) in PDAC have received more attention in recent years. As increasing evidence suggests the heterogeneity of CAFs in PDAC, different CAF subtypes have been shown to support tumor growth, while others suppress cancer proliferation. Myofibrotic CAFs (myCAFs) show alpha-smooth muscle actin (α-SMA)high interleukin-6 (IL-6)low myofibroblastic features, are activated by direct contact with tumor cells, and are located in the periglandular region. Inflammatory CAFs (iCAFs) show α-SMAlow IL-6high inflammatory features, are activated by paracrine factors secreted from tumor cells, and are located away from cancer cells. Antigen-presenting CAFs (apCAFs) show major histocompatibility complex II (MHC II) family genes that are highly expressed. CAFs have also been gradually explored as diagnostic and prognostic markers in pancreatic cancer. Targeted therapy of CAFs in PDAC has gradually attracted attention. With the deepening of related studies, some meaningful positive and negative results have surfaced, and CAFs may be the key to unlocking the door to pancreatic cancer treatment. Our review summarizes recent advances in the heterogeneity, function, and markers of CAFs in pancreatic cancer, as well as research and treatment targeting CAFs in pancreatic cancer. |
| first_indexed | 2024-12-17T01:50:00Z |
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| id | doaj.art-f68457a77842488f94c78ed51512232a |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-17T01:50:00Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-f68457a77842488f94c78ed51512232a2022-12-21T22:08:05ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-07-01910.3389/fcell.2021.655152655152Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic CancerXinglong Geng0Xinglong Geng1Xinglong Geng2Hongze Chen3Hongze Chen4Liang Zhao5Jisheng Hu6Jisheng Hu7Wenbo Yang8Wenbo Yang9Guanqun Li10Guanqun Li11Chundong Cheng12Chundong Cheng13Zhongjie Zhao14Zhongjie Zhao15Tao Zhang16Tao Zhang17Le Li18Le Li19Bei Sun20Bei Sun21Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Abdominal Endoscopic Surgery, Affiliated Hospital of Qinghai University, Xining, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Gynecology, Qinghai University Affiliated Hospital, Xining, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaKey Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that typically features a dramatic desmoplastic reaction, especially fibroblasts. The roles of cancer-associated fibroblasts (CAFs) in PDAC have received more attention in recent years. As increasing evidence suggests the heterogeneity of CAFs in PDAC, different CAF subtypes have been shown to support tumor growth, while others suppress cancer proliferation. Myofibrotic CAFs (myCAFs) show alpha-smooth muscle actin (α-SMA)high interleukin-6 (IL-6)low myofibroblastic features, are activated by direct contact with tumor cells, and are located in the periglandular region. Inflammatory CAFs (iCAFs) show α-SMAlow IL-6high inflammatory features, are activated by paracrine factors secreted from tumor cells, and are located away from cancer cells. Antigen-presenting CAFs (apCAFs) show major histocompatibility complex II (MHC II) family genes that are highly expressed. CAFs have also been gradually explored as diagnostic and prognostic markers in pancreatic cancer. Targeted therapy of CAFs in PDAC has gradually attracted attention. With the deepening of related studies, some meaningful positive and negative results have surfaced, and CAFs may be the key to unlocking the door to pancreatic cancer treatment. Our review summarizes recent advances in the heterogeneity, function, and markers of CAFs in pancreatic cancer, as well as research and treatment targeting CAFs in pancreatic cancer.https://www.frontiersin.org/articles/10.3389/fcell.2021.655152/fullcancer-associated fibroblastsheterogeneitypancreatic cancerhallmarkdiagnosisprognosis |
| spellingShingle | Xinglong Geng Xinglong Geng Xinglong Geng Hongze Chen Hongze Chen Liang Zhao Jisheng Hu Jisheng Hu Wenbo Yang Wenbo Yang Guanqun Li Guanqun Li Chundong Cheng Chundong Cheng Zhongjie Zhao Zhongjie Zhao Tao Zhang Tao Zhang Le Li Le Li Bei Sun Bei Sun Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer Frontiers in Cell and Developmental Biology cancer-associated fibroblasts heterogeneity pancreatic cancer hallmark diagnosis prognosis |
| title | Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer |
| title_full | Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer |
| title_fullStr | Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer |
| title_full_unstemmed | Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer |
| title_short | Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer |
| title_sort | cancer associated fibroblast caf heterogeneity and targeting therapy of cafs in pancreatic cancer |
| topic | cancer-associated fibroblasts heterogeneity pancreatic cancer hallmark diagnosis prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.655152/full |
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