TY - JOUR
T1 - Understanding the Bone in Cancer Metastasis
AU - Fornetti, Jaime
AU - Welm, Alana L.
AU - Stewart, Sheila A.
N1 - Funding Information:
This work was supported by Susan G. Komen Postdoctoral Fellowship PDF16376311 to JF; ALW is supported by the U.S. Department of Defense Era of Hope Scholar Award (BC112623), the NIH National Cancer Institute (1R01CA166422, P30CA042014, and 1U54CA22407), the Susan G. Komen Foundation (SAC160078), and the Breast Cancer Research Foundation (102182510); SAS is supported by the NIH National Cancer Institute (R01CA217208-01A1), NIH National Institute of Aging (RO1AG059244-01), and the U.S. Army Medical Research Acquisition Activity (820 Chandler Street, Fort Detrick, MD 21702-5014, USA), which is the awarding and administrating acquisition office, and this was supported in part by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program, under award No. W81XWH-16-1-0728. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. We thank members of the Stewart and Welm laboratories for useful discussions.
Funding Information:
This work was supported by Susan G. Komen Postdoctoral Fellowship PDF16376311 to JF; ALW is supported by the U.S. Department of Defense Era of Hope Scholar Award (BC112623), the NIH National Cancer Institute (1R01CA166422, P30CA042014, and 1U54CA22407), the Susan G. Komen Foundation (SAC160078), and the Breast Cancer Research Foundation (102182510); SAS is supported by the NIH National Cancer Institute (R01CA217208-01A1), NIH National Institute of Aging (RO1AG059244-01), and the U.S. Army Medical Research Acquisition Activity (820 Chandler Street, Fort Detrick, MD 21702-5014, USA), which is the awarding and administrating acquisition office, and this was supported in part by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program, under award No. W81XWH-16-1-0728. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. We thank members of the Stewart and Welm laboratories for useful discussions. Authors? roles: JF and SAS contributed to the conception, writing, and revision of the manuscript; ALW contributed to the conception and revision.
Publisher Copyright:
© 2018 American Society for Bone and Mineral Research
PY - 2018/12
Y1 - 2018/12
N2 - The bone is the third most common site of metastasis for a wide range of solid tumors including lung, breast, prostate, colorectal, thyroid, gynecologic, and melanoma, with 70% of metastatic prostate and breast cancer patients harboring bone metastasis.1 Unfortunately, once cancer spreads to the bone, it is rarely cured and is associated with a wide range of morbidities including pain, increased risk of fracture, and hypercalcemia. This fact has driven experts in the fields of bone and cancer biology to study the bone, and has revealed that there is a great deal that each can teach the other. The complexity of the bone was first described in 1889 when Stephen Paget proposed that tumor cells have a proclivity for certain organs, where they “seed” into a friendly “soil” and eventually grow into metastatic lesions. Dr. Paget went on to argue that although many study the “seed” it would be paramount to understand the “soil.” Since this original work, significant advances have been made not only in understanding the cell-autonomous mechanisms that drive metastasis, but also alterations which drive changes to the “soil” that allow a tumor cell to thrive. Indeed, it is now clear that the “soil” in different metastatic sites is unique, and thus the mechanisms that allow tumor cells to remain in a dormant or growing state are specific to the organ in question. In the bone, our knowledge of the components that contribute to this fertile “soil” continues to expand, but our understanding of how they impact tumor growth in the bone remains in its infancy. Indeed, we now appreciate that the endosteal niche likely contributes to tumor cell dormancy, and that osteoclasts, osteocytes, and adipocytes can impact tumor cell growth. Here, we discuss the bone microenvironment and how it impacts cancer cell seeding, dormancy, and growth.
AB - The bone is the third most common site of metastasis for a wide range of solid tumors including lung, breast, prostate, colorectal, thyroid, gynecologic, and melanoma, with 70% of metastatic prostate and breast cancer patients harboring bone metastasis.1 Unfortunately, once cancer spreads to the bone, it is rarely cured and is associated with a wide range of morbidities including pain, increased risk of fracture, and hypercalcemia. This fact has driven experts in the fields of bone and cancer biology to study the bone, and has revealed that there is a great deal that each can teach the other. The complexity of the bone was first described in 1889 when Stephen Paget proposed that tumor cells have a proclivity for certain organs, where they “seed” into a friendly “soil” and eventually grow into metastatic lesions. Dr. Paget went on to argue that although many study the “seed” it would be paramount to understand the “soil.” Since this original work, significant advances have been made not only in understanding the cell-autonomous mechanisms that drive metastasis, but also alterations which drive changes to the “soil” that allow a tumor cell to thrive. Indeed, it is now clear that the “soil” in different metastatic sites is unique, and thus the mechanisms that allow tumor cells to remain in a dormant or growing state are specific to the organ in question. In the bone, our knowledge of the components that contribute to this fertile “soil” continues to expand, but our understanding of how they impact tumor growth in the bone remains in its infancy. Indeed, we now appreciate that the endosteal niche likely contributes to tumor cell dormancy, and that osteoclasts, osteocytes, and adipocytes can impact tumor cell growth. Here, we discuss the bone microenvironment and how it impacts cancer cell seeding, dormancy, and growth.
KW - AGING IN THE BONE MICROENVIRONMENT
KW - BONE NICHE
KW - BONE TURNOVER
KW - CANCER-BONE CROSSTALK
KW - METASTASIS
KW - TUMOR CELL DORMANCY
UR - http://www.scopus.com/inward/record.url?scp=85057474242&partnerID=8YFLogxK
U2 - 10.1002/jbmr.3618
DO - 10.1002/jbmr.3618
M3 - Review article
C2 - 30476357
AN - SCOPUS:85057474242
VL - 33
SP - 2099
EP - 2113
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 12
ER -