Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated?
Pancreatic ductal adenocarcinoma is characterized by an extensive stromal response called desmoplasia. Within the tumor stroma, cancer-associated fibroblasts (CAFs) are the primary cell type. CAFs have been shown to play a role in pancreatic cancer progression; they secrete growth factors, inflammat...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2018-12-01
|
| Series: | Integrative Cancer Therapies |
| Online Access: | https://doi.org/10.1177/1534735418794884 |
| _version_ | 1818585192972943360 |
|---|---|
| author | Chao Qu PhD Qing Wang MD Zhiqiang Meng PhD Peng Wang PhD |
| author_facet | Chao Qu PhD Qing Wang MD Zhiqiang Meng PhD Peng Wang PhD |
| author_sort | Chao Qu PhD |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma is characterized by an extensive stromal response called desmoplasia. Within the tumor stroma, cancer-associated fibroblasts (CAFs) are the primary cell type. CAFs have been shown to play a role in pancreatic cancer progression; they secrete growth factors, inflammatory cytokines, and chemokines that stimulate signaling pathways in cancer cells and modulate the cancer biology toward increased aggressiveness. Therefore, targeting CAFs may serve as a powerful weapon against pancreatic cancer and improve therapeutic effects. However, a previous study aiming to deplete CAFs by inhibiting sonic Hedgehog signaling failed to show any benefit in survival time of pancreatic cancer patients. We reported that the natural product curcumin reeducated CAFs in pancreatic cancer treatment. A low concentration of curcumin reversed the activation of fibroblasts without exhibiting growth suppression effects. In addition, curcumin suppressed CAF-induced pancreatic cancer cell migration and invasion in vitro and lung metastasis in vivo. The results of our study suggest that active CAFs can be inactivated by certain natural products such as curcumin. Reeducation of CAFs back to their normal state, rather than their indiscriminate depletion, may broaden our view in the development of therapeutic options for the treatment of pancreatic cancer. |
| first_indexed | 2024-12-16T08:33:10Z |
| format | Article |
| id | doaj.art-70fde609dc11408cba0d104bfd93adb8 |
| institution | Directory Open Access Journal |
| issn | 1534-7354 1552-695X |
| language | English |
| last_indexed | 2024-12-16T08:33:10Z |
| publishDate | 2018-12-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Integrative Cancer Therapies |
| spelling | doaj.art-70fde609dc11408cba0d104bfd93adb82022-12-21T22:37:49ZengSAGE PublishingIntegrative Cancer Therapies1534-73541552-695X2018-12-011710.1177/1534735418794884Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated?Chao Qu PhD0Qing Wang MD1Zhiqiang Meng PhD2Peng Wang PhD3Shanghai Medical College, Fudan University, Shanghai, ChinaHuashan Hospital, Fudan University, Shanghai, ChinaShanghai Medical College, Fudan University, Shanghai, ChinaShanghai Medical College, Fudan University, Shanghai, ChinaPancreatic ductal adenocarcinoma is characterized by an extensive stromal response called desmoplasia. Within the tumor stroma, cancer-associated fibroblasts (CAFs) are the primary cell type. CAFs have been shown to play a role in pancreatic cancer progression; they secrete growth factors, inflammatory cytokines, and chemokines that stimulate signaling pathways in cancer cells and modulate the cancer biology toward increased aggressiveness. Therefore, targeting CAFs may serve as a powerful weapon against pancreatic cancer and improve therapeutic effects. However, a previous study aiming to deplete CAFs by inhibiting sonic Hedgehog signaling failed to show any benefit in survival time of pancreatic cancer patients. We reported that the natural product curcumin reeducated CAFs in pancreatic cancer treatment. A low concentration of curcumin reversed the activation of fibroblasts without exhibiting growth suppression effects. In addition, curcumin suppressed CAF-induced pancreatic cancer cell migration and invasion in vitro and lung metastasis in vivo. The results of our study suggest that active CAFs can be inactivated by certain natural products such as curcumin. Reeducation of CAFs back to their normal state, rather than their indiscriminate depletion, may broaden our view in the development of therapeutic options for the treatment of pancreatic cancer.https://doi.org/10.1177/1534735418794884 |
| spellingShingle | Chao Qu PhD Qing Wang MD Zhiqiang Meng PhD Peng Wang PhD Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated? Integrative Cancer Therapies |
| title | Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated? |
| title_full | Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated? |
| title_fullStr | Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated? |
| title_full_unstemmed | Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated? |
| title_short | Cancer-Associated Fibroblasts in Pancreatic Cancer: Should They Be Deleted or Reeducated? |
| title_sort | cancer associated fibroblasts in pancreatic cancer should they be deleted or reeducated |
| url | https://doi.org/10.1177/1534735418794884 |
| work_keys_str_mv | AT chaoquphd cancerassociatedfibroblastsinpancreaticcancershouldtheybedeletedorreeducated AT qingwangmd cancerassociatedfibroblastsinpancreaticcancershouldtheybedeletedorreeducated AT zhiqiangmengphd cancerassociatedfibroblastsinpancreaticcancershouldtheybedeletedorreeducated AT pengwangphd cancerassociatedfibroblastsinpancreaticcancershouldtheybedeletedorreeducated |