Aberrant Activation of Wound-Healing Programs within the Metastatic Niche Facilitates Lung Colonization by Osteosarcoma Cells
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Osteosarcoma lung metastasis is driven by fibrosis. The antifibrotic drug nintedanib effectively blocks this progression by targeting the tumor microenvironment, offering a new therapeutic strategy.
Area Of Science
- Oncology
- Pulmonary Medicine
- Translational Research
Background
- Lung metastasis is the primary cause of mortality in osteosarcoma, a common pediatric bone cancer.
- The mechanisms by which osteosarcoma cells create a supportive lung microenvironment for metastasis are not fully understood.
Purpose Of The Study
- To identify therapeutic vulnerabilities specific to osteosarcoma metastasis.
- To elucidate the cellular and molecular mechanisms of osteosarcoma lung metastatic niche formation.
Main Methods
- Single-cell RNA sequencing and spatial transcriptomics were employed to analyze molecular changes in lung tissues from murine models and human samples.
- Multiparameter immunofluorescence confirmed transcriptomic findings at the protein level.
- Nintedanib efficacy was evaluated in murine and human xenograft models of osteosarcoma lung metastasis.
Main Results
- Osteosarcoma cell dissemination induced acute alveolar epithelial injury and a chronic, nonresolving wound-healing phenotype in the lung stroma.
- Metastasis-associated lungs exhibited significant fibrosis due to profibrotic epithelial cells and macrophages.
- Nintedanib treatment inhibited osteosarcoma-induced fibrosis and prevented metastatic progression in preclinical models.
Conclusions
- Lung fibrosis is a critical, targetable vulnerability in osteosarcoma metastasis.
- Interactions between osteosarcoma cells and lung epithelial cells promote a prometastatic niche via extracellular matrix deposition.
- Nintedanib, a tyrosine kinase inhibitor, disrupts this niche by inhibiting fibrosis, highlighting non-cell-autonomous effects of TKIs in metastasis.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
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...
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...