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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
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Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
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Mesenchymal stroma: Role in osteosarcoma progression.

Margherita Cortini1, Sofia Avnet2, Nicola Baldini1

  • 1Orthopaedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

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The tumor microenvironment, including mesenchymal stromal cells, significantly drives osteosarcoma progression. Understanding these interactions offers potential for new sarcoma therapies.

Keywords:
Extracellular vesiclesIL-6Mesenchymal stromaMetabolitesMicroenvironmentOsteosarcoma

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Area of Science:

  • Oncology
  • Cancer Biology
  • Tumor Microenvironment Research

Background:

  • Malignant tumor growth and metastasis depend on the tumor microenvironment, not solely cancer cells.
  • The tumor microenvironment comprises various cells (cancer stem cells, immune cells, fibroblasts) interacting under physical and biochemical stimuli.
  • Mesenchymal stromal cells play a critical role in osteosarcoma progression, a challenging cancer in young adults.

Purpose of the Study:

  • To review the contribution of the stroma, particularly mesenchymal stroma, to osteosarcoma progression.
  • To highlight the mechanisms by which mesenchymal stromal cells influence osteosarcoma, including homing, neovascularization, and immune modulation.
  • To discuss recent advances in molecular signaling between stromal and osteosarcoma cells for therapeutic insights.

Main Methods:

  • Review of recent scientific literature on osteosarcoma and its microenvironment.
  • Analysis of the roles of mesenchymal stromal cells and their interactions with osteosarcoma cells.
  • Synthesis of molecular cues, cytokines, and metabolites involved in stromal-osteosarcoma axis.

Main Results:

  • Mesenchymal stromal cells contribute to osteosarcoma progression via homing, neovascularization, paracrine signaling, and immune modulation.
  • Tumor cells induce microenvironmental changes that mesenchymal stromal cells respond to, further aiding tumor growth.
  • Extracellular vesicles and soluble factors mediate crucial interactions within the osteosarcoma microenvironment.

Conclusions:

  • The mesenchymal stroma is a key player in osteosarcoma progression, offering therapeutic targets.
  • Understanding the molecular interplay between stromal cells and osteosarcoma cells is vital for developing novel treatment strategies.
  • Targeting stromal components and their signaling pathways may lead to more effective therapies for osteosarcoma and other sarcomas.