A phenomenon many of us have always wondered about is: when patients are in their final stages of cancer, why do they lose their appetite and waste away? Although the tumor might remain localized to one organ/tissue, while many other cancers spread (metastasize) throughout the body –– this loss of apetite (anorexia) and wasting away (cachexia) usually happens in both cases. It must be kept in mind that tumor growth and malignant progression rely not only on the intrinsic aberrant genetic and epigenetic make-up of tumor cells, but also on tumor-induced systemic factors that affect not only cells in the primary tumor but also distant microenvironments. In recent years, bone marrow–derived cells (BMDCs) have been shown to contribute to primary tumor progression by promoting hallmark processes such as inflammation, immunosuppression, vasculogenesis, and extracellular matrix remodeling.
BMDCs are also involved in establishing tumor-permissive microenvironments that form –– before the arrival of disseminated tumor cells at future metastatic sites (known as premetastatic niches) and promote metastatic outgrowth. In addition to the direct effects of tumor-secreted factors on BMDC recruitment to tumors, authors [attached report] show that osteoblasts, which reside in the bone, can be remotely activated by secreted factors from lung adenocarcinoma, which, in turn, mobilize a specific subset of BMDCs — neutrophils — to foster tumor growth. And the signaling molecules that actually are resonsible –– in BMDCs and neutrophils –– undoubtedly include cytokines, chemokines, and lipid mediators (which include prostaglandins, prostacyclins, thromboxanes, lipoxins, eicosanoids, resolvins, docosatrienes, neuroprotectins –– all in all, a total of more than 150 types of 2nd-messenger signaling molecules).
This attached study identifies systemic cross-talk between lung tumors and myeloid cells of bone marrow: Lung tumors can remotely activate specific types of osteoblast cells in bones. In turn, these osteoblasts supply tumors with a subset type of neutrophils, which foster cancer progression. Authors show, in mice and in cancer patients that lung adenocarcinomas increase bone stromal activity in the absence of bone metastasis..!! Animal studies revealed that the cancer-induced bone phenotype involves bone-resident osteocalcin-expressing (Ocn+) osteoblastic cells. These cells stimulate cancer by remotely supplying a distinct subset of tumor-infiltrating SiglecFhigh neutrophils, which exhibit cancer-promoting properties. Experimentally reducing Ocn+ cell numbers suppresses the neutrophil response and lung tumor outgrowth. These exciting findings postulate that osteoblasts are remote regulators of lung cancer and identify SiglecFhigh neutrophils as myeloid cell effectors of the osteoblast-driven pro-tumoral response.
Science 1 Dec 2o17; 358: 1147 (one page article) & editorial pp 1127–1128