Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis
Bone-metastatic prostate cancer is common in men with recurrent castrate-resistant disease. To date, therapeutic focus has largely revolved around androgen deprivation therapy (ADT) and chemotherapy. While second-generation ADTs and combination ADT/chemotherapy approaches have been successful in ext...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2018.00247/full |
| _version_ | 1811207741249683456 |
|---|---|
| author | Chen Hao Lo Chen Hao Lo Conor C. Lynch |
| author_facet | Chen Hao Lo Chen Hao Lo Conor C. Lynch |
| author_sort | Chen Hao Lo |
| collection | DOAJ |
| description | Bone-metastatic prostate cancer is common in men with recurrent castrate-resistant disease. To date, therapeutic focus has largely revolved around androgen deprivation therapy (ADT) and chemotherapy. While second-generation ADTs and combination ADT/chemotherapy approaches have been successful in extending overall survival, the disease remains incurable. It is clear that molecular and cellular components of the cancer-bone microenvironment contribute to the disease progression and potentially to the emergence of therapy resistance. In bone, metastatic prostate cancer cells manipulate bone-forming osteoblasts and bone-resorbing osteoclasts to produce growth and survival factors. While osteoclast-targeted therapies such as bisphosphonates have improved quality of life, emerging data have defined important roles for additional cells of the bone microenvironment, including macrophages and T cells. Disappointingly, early clinical trials with checkpoint blockade inhibitors geared at promoting cytotoxic T cell response have not proved as promising for prostate cancer compared to other solid malignancies. Macrophages, including bone-resident osteomacs, are a major component of the bone marrow and play key roles in coordinating normal bone remodeling and injury repair. The role for anti-inflammatory macrophages in the progression of primary prostate cancer is well established yet relatively little is known about macrophages in the context of bone-metastatic prostate cancer. The focus of the current review is to summarize our knowledge of macrophage contribution to normal bone remodeling and prostate-to-bone metastasis, while also considering the impact of standard of care and targeted therapies on macrophage behavior in the tumor-bone microenvironment. |
| first_indexed | 2024-04-12T04:08:30Z |
| format | Article |
| id | doaj.art-576bbf3d0fd54cee9e4f438dd613d50a |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T04:08:30Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-576bbf3d0fd54cee9e4f438dd613d50a2022-12-22T03:48:33ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-05-01910.3389/fendo.2018.00247367766Multifaceted Roles for Macrophages in Prostate Cancer Skeletal MetastasisChen Hao Lo0Chen Hao Lo1Conor C. Lynch2Cancer Biology Program, University of South Florida, Tampa, FL, United StatesTumor Biology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United StatesTumor Biology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United StatesBone-metastatic prostate cancer is common in men with recurrent castrate-resistant disease. To date, therapeutic focus has largely revolved around androgen deprivation therapy (ADT) and chemotherapy. While second-generation ADTs and combination ADT/chemotherapy approaches have been successful in extending overall survival, the disease remains incurable. It is clear that molecular and cellular components of the cancer-bone microenvironment contribute to the disease progression and potentially to the emergence of therapy resistance. In bone, metastatic prostate cancer cells manipulate bone-forming osteoblasts and bone-resorbing osteoclasts to produce growth and survival factors. While osteoclast-targeted therapies such as bisphosphonates have improved quality of life, emerging data have defined important roles for additional cells of the bone microenvironment, including macrophages and T cells. Disappointingly, early clinical trials with checkpoint blockade inhibitors geared at promoting cytotoxic T cell response have not proved as promising for prostate cancer compared to other solid malignancies. Macrophages, including bone-resident osteomacs, are a major component of the bone marrow and play key roles in coordinating normal bone remodeling and injury repair. The role for anti-inflammatory macrophages in the progression of primary prostate cancer is well established yet relatively little is known about macrophages in the context of bone-metastatic prostate cancer. The focus of the current review is to summarize our knowledge of macrophage contribution to normal bone remodeling and prostate-to-bone metastasis, while also considering the impact of standard of care and targeted therapies on macrophage behavior in the tumor-bone microenvironment.https://www.frontiersin.org/article/10.3389/fendo.2018.00247/fullboneprostate cancermetastasismacrophagepolarizationtherapy |
| spellingShingle | Chen Hao Lo Chen Hao Lo Conor C. Lynch Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis Frontiers in Endocrinology bone prostate cancer metastasis macrophage polarization therapy |
| title | Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis |
| title_full | Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis |
| title_fullStr | Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis |
| title_full_unstemmed | Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis |
| title_short | Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis |
| title_sort | multifaceted roles for macrophages in prostate cancer skeletal metastasis |
| topic | bone prostate cancer metastasis macrophage polarization therapy |
| url | https://www.frontiersin.org/article/10.3389/fendo.2018.00247/full |
| work_keys_str_mv | AT chenhaolo multifacetedrolesformacrophagesinprostatecancerskeletalmetastasis AT chenhaolo multifacetedrolesformacrophagesinprostatecancerskeletalmetastasis AT conorclynch multifacetedrolesformacrophagesinprostatecancerskeletalmetastasis |