Matricellular proteins tune myeloid-derived suppressor cell recruitment and function in breast cancer

Abstract

Solid tumor progression is often associated with the expansion of myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells that actively foster tumor growth and metastatic dissemination through a plethora of mechanisms, including, but not limited to, their major suppressive activity on the immune response. Indeed, MDSCs may sustain tumor progression by dynamically remodeling the tumor microenvironment through the production of angiogenic factors and metalloproteases, by helping the establishment of a premetastatic niche, and by promoting stemness and epithelial-to-mesenchymal transition (EMT) features in tumor cells. MDSCs are also regulated by a growing list of factors that mainly comprise 2 sets of signals: those responsible for their expansion and recruitment, such as GM-, M-, and G-CSF and other growth factors, and those relevant for the induction of their suppressive activity, which include proinflammatory cytokines and transcription factors. We review here a new class of MDSC regulators-matricellular proteins-with a particular focus on osteopontin (OPN) and secreted acidic cysteine-rich glycoprotein (SPARC), which seem to affect the expansion/recruitment and the immune-suppressive activity of MDSCs. Matricellular proteins function indirectly on MDSCs through the induction of other mediators when produced by tumor cells and cell autonomously when expressed-likely in an intracellular form-directly by MDSCs.

Regulation of heterotopic ossification by monocytes in a mouse model of aberrant wound healing

“…We observed temporal changes in these subpopulations over the course of the inflammatory response that indicate a close interaction with mesenchymal progenitor cells leading to aberrant healing. While immune modulating therapies have become a mainstay in cancer therapies, they have failed to translate to diseases of nononcogenic aberrant cell fate [36][37][38][39] . Here, we have validated a therapeutic approach that modulates the macrophage phenotype to prevent aberrant musculoskeletal regeneration in a model of HO.…”

Role of osteopontin in dendritic cell shaping of immune responses

“…For example, TAMs interacting with colorectal cancer stem cells by secreting OPN, promote tumorigenicity and clonogenicity [103]. OPN has also a role of in the expansion and activitiy of MDSCs [104,105]. In a mouse model of metastatic breast cancer, both tumor-and myeloid-derived OPN contribute to metastatic progression.…”

Regulation of heterotopic ossification through local inflammatory monocytes in a mouse model of aberrant wound healing

“…We observed temporal changes in these subpopulations over the course of the inflammatory response that indicate a close interaction with mesenchymal progenitor cells leading to aberrant healing. While immune modulating therapies have become a mainstay in cancer therapies, they have failed to translate to diseases of non-oncogenic aberrant cell fate [36][37][38][39] . Here, we have validated a therapeutic approach that modulates the macrophage phenotype to prevent aberrant musculoskeletal regeneration in a model of HO.…”