Bone Marrow Adipose Tissue: A New Player in Cancer Metastasis to Bone

Abstract

The bone marrow is a favored site for a number of cancers, including the hematological malignancy multiple myeloma, and metastasis of breast and prostate cancer. This specialized microenvironment is highly supportive, not only for tumor growth and survival but also for the development of an associated destructive cancer-induced bone disease. The interactions between tumor cells, osteoclasts and osteoblasts are well documented. By contrast, despite occupying a significant proportion of the bone marrow, the importance of bone marrow adipose tissue is only just emerging. The ability of bone marrow adipocytes to regulate skeletal biology and hematopoiesis, combined with their metabolic activity, endocrine functions, and proximity to tumor cells means that they are ideally placed to impact both tumor growth and bone disease. This review discusses the recent advances in our understanding of how marrow adipose tissue contributes to bone metastasis and cancer-induced bone disease.

MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells

“…A mutually incompatible relationship arises between adipose components of the BM and bone-forming components, as osteoblastogenesis and the factors that support it often inhibit adipogenesis, and vice versa. This is consistent with the inhibition of bone formation often performed by BMAT [21]. This may be due to direct effects of these cells on each other or could be due to lineage competition that results from the fact that both osteoblasts and adipocytes derive from the same precursor cell.…”

“…A key regulator of skeletal biology, hematopoiesis, and metabolic activity, BMAT is also involved in endocrine functions and the secretion of fatty acids, chemokines, and adipokines [21]. BMAT volume increases with age and occupies a significant portion of the BM, as well as composing over 10% of the average person's total adipose tissue mass [21].…”

“…A key regulator of skeletal biology, hematopoiesis, and metabolic activity, BMAT is also involved in endocrine functions and the secretion of fatty acids, chemokines, and adipokines [21]. BMAT volume increases with age and occupies a significant portion of the BM, as well as composing over 10% of the average person's total adipose tissue mass [21]. Of significance to this review is the finding that elevated regulated BMAT volume, which is located in close proximity to the trabecular bone and hematopoietic elements and increases with age, is directly correlated with bone loss and resultant osteoporosis [22].…”

“…BMAT accumulation, which is most often due to aging, obesity, and radiation, may also be a contributor to cancer, osteoporosis, and bone disease [1]. Seventy to 80% of advanced cases of breast and prostate cancer, tumor cells migrate to and occupy the BM niche, and BMAT may contribute to the fertile soil for tumor growth they encounter there [21]. Specifically, it is very likely that BM adipocytes influence the microenvironment by secreting extracellular vesicles that contain adipogenic mRNA transcripts which could then be taken up by osteoblasts or cancer cells [21].…”

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite

“…Indeed, they secrete a large panel of bioactive molecules, named adipokines, including hormones, growth factors, chemokines and pro-inflammatory molecules, whose balance is perturbed in obesity (123,124). Due to the distribution of adipose tissue (AT), many cancer cells will come into contact with adipocytes during local invasion (for example in breast, colon and prostate cancers, as well as melanoma) but also distant dissemination (to the omental fat for gastric and ovarian cancer, but also to the bone marrow) (125,126). Using a coculture system, we have demonstrated that adipocytes cultivated with cancer cells display a modified phenotype, with decreased lipid content and downregulation of adipocyte markers.…”