Bone Metastasis
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Roodman (April 15 issue)1 stated that in osteolytic metastases, the destruction of bone is mediated by osteoclasts rather than tumor cells, whereas the mechanisms of osteoblastic metastases and the factors involved are unknown. It would be helpful if he would put these new concepts into perspective in relation to traditional observations.
Is there no place for the conventional view that metastases can cause osseous destruction simply because of tumor replacement of bone, as appears to happen in metastases to other tissues, such as the liver, or at the primary tumor site? This view is in keeping with the facts that more aggressive tumors usually have more lytic osseous metastases and that in tumors rendered less aggressive by treatment, the lytic bone metastases often become blastic.
Prostate and carcinoid tumors have been thought, intuitively, to cause osteoblastic metastases, because their slow growth allows more time for woven bone repair. In addition, well-differentiated tumors like these are presumably more capable of producing and secreting substances than are poorly differentiated tumors, and it has long been speculated that such well-differentiated tumors might produce some bone-stimulating factor.
Ferris M. Hall, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
fhall@bidmc.harvard.edu
References
Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-1664.
Dr. Roodman replies: Dr. Hall asks whether tumor replacement and rapid growth of tumors in bone cause osteolysis, whereas less aggressive tumors are osteoblastic. Tumors can induce bone resorption in vitro by releasing hydrolytic enzymes.1 However, studies in vitro and in vivo have clearly shown that the chief mechanism responsible for tumor-induced bone destruction is increased formation of osteoclasts. Replacement of marrow by tumor does not explain osteolysis, since lymphomas can replace marrow but do not usually cause lytic lesions.
Dr. Hall suggests that when tumors are rendered less aggressive by chemotherapy, the lesions become osteoblastic because there is sufficient time in which large amounts of woven bone may form. Although this is an interesting hypothesis, the ratio of bone-resorbing factors to bone-forming factors produced in the microenvironment of bone tumor determines whether the lesion is lytic or blastic. Although the factors responsible for osteoblastic metastasis have not been definitively identified, several bone-inducing factors that are produced by breast-cancer cells or prostate-cancer cells, such as endothelin-1 and adrenomedullin, have been suggested as mediators of osteoblastic metastasis in tumor models.2,3
G. David Roodman, M.D., Ph.D.
University of Pittsburgh
Pittsburgh, PA 15213
roodmangd@msx.upms.edu
References
Eilon G, Mundy GR. Association of increased cyclic adenosine 3':5'-monophosphate content in cultured human breast cancer cells and release of hydrolytic enzymes and bone-resorbing activity. Cancer Res 1983;43:5792-5794.
Cornish J, Naot D. Amylin and adrenomedullin: novel regulators of bone growth. Curr Pharm Des 2002;8:2009-2021.
Guise TA, Mohammad KS. Endothelins in bone cancer metastases. Cancer Treat Res 2004;118:197-212.
Is there no place for the conventional view that metastases can cause osseous destruction simply because of tumor replacement of bone, as appears to happen in metastases to other tissues, such as the liver, or at the primary tumor site? This view is in keeping with the facts that more aggressive tumors usually have more lytic osseous metastases and that in tumors rendered less aggressive by treatment, the lytic bone metastases often become blastic.
Prostate and carcinoid tumors have been thought, intuitively, to cause osteoblastic metastases, because their slow growth allows more time for woven bone repair. In addition, well-differentiated tumors like these are presumably more capable of producing and secreting substances than are poorly differentiated tumors, and it has long been speculated that such well-differentiated tumors might produce some bone-stimulating factor.
Ferris M. Hall, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
fhall@bidmc.harvard.edu
References
Roodman GD. Mechanisms of bone metastasis. N Engl J Med 2004;350:1655-1664.
Dr. Roodman replies: Dr. Hall asks whether tumor replacement and rapid growth of tumors in bone cause osteolysis, whereas less aggressive tumors are osteoblastic. Tumors can induce bone resorption in vitro by releasing hydrolytic enzymes.1 However, studies in vitro and in vivo have clearly shown that the chief mechanism responsible for tumor-induced bone destruction is increased formation of osteoclasts. Replacement of marrow by tumor does not explain osteolysis, since lymphomas can replace marrow but do not usually cause lytic lesions.
Dr. Hall suggests that when tumors are rendered less aggressive by chemotherapy, the lesions become osteoblastic because there is sufficient time in which large amounts of woven bone may form. Although this is an interesting hypothesis, the ratio of bone-resorbing factors to bone-forming factors produced in the microenvironment of bone tumor determines whether the lesion is lytic or blastic. Although the factors responsible for osteoblastic metastasis have not been definitively identified, several bone-inducing factors that are produced by breast-cancer cells or prostate-cancer cells, such as endothelin-1 and adrenomedullin, have been suggested as mediators of osteoblastic metastasis in tumor models.2,3
G. David Roodman, M.D., Ph.D.
University of Pittsburgh
Pittsburgh, PA 15213
roodmangd@msx.upms.edu
References
Eilon G, Mundy GR. Association of increased cyclic adenosine 3':5'-monophosphate content in cultured human breast cancer cells and release of hydrolytic enzymes and bone-resorbing activity. Cancer Res 1983;43:5792-5794.
Cornish J, Naot D. Amylin and adrenomedullin: novel regulators of bone growth. Curr Pharm Des 2002;8:2009-2021.
Guise TA, Mohammad KS. Endothelins in bone cancer metastases. Cancer Treat Res 2004;118:197-212.