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Sökning: WFRF:(Lehti K) > Gonzalez Molina J

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  • Pietila, EA, et al. (författare)
  • Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3904-
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to its dynamic nature, the evolution of cancer cell-extracellular matrix (ECM) crosstalk, critically affecting metastasis and treatment resistance, remains elusive. Our results show that platinum-chemotherapy itself enhances resistance by progressively changing the cancer cell-intrinsic adhesion signaling and cell-surrounding ECM. Examining ovarian high-grade serous carcinoma (HGSC) transcriptome and histology, we describe the fibrotic ECM heterogeneity at primary tumors and distinct metastatic sites, prior and after chemotherapy. Using cell models from systematic ECM screen to collagen-based 2D and 3D cultures, we demonstrate that both specific ECM substrates and stiffness increase resistance to platinum-mediated, apoptosis-inducing DNA damage via FAK and β1 integrin-pMLC-YAP signaling. Among such substrates around metastatic HGSCs, COL6 was upregulated by chemotherapy and enhanced the resistance of relapse, but not treatment-naïve, HGSC organoids. These results identify matrix adhesion as an adaptive response, driving HGSC aggressiveness via co-evolving ECM composition and sensing, suggesting stromal and tumor strategies for ECM pathway targeting.
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  • Gonzalez-Molina, J, et al. (författare)
  • MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues
  • 2019
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 8:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Sarcomas are deadly malignant tumors of mesenchymal origin occurring at all ages. The expression and function of the membrane-type matrix metalloproteinase MMP14 is closely related to the mesenchymal cell phenotype, and it is highly expressed in most sarcomas. MMP14 regulates the activity of multiple extracellular and plasma membrane proteins, influencing cell–cell and cell–extracellular matrix (ECM) communication. This regulation mediates processes such as ECM degradation and remodeling, cell invasion, and cancer metastasis. Thus, a comprehensive understanding of the biology of MMP14 in sarcomas will shed light on the mechanisms controlling the key processes in these diseases. Here, we provide an overview of the function and regulation of MMP14 and we discuss their relationship with clinical and pre-clinical MMP14 data in both adult and childhood sarcomas.
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