Researchers from Karolinska Institutet have discovered how platinum-chemotherapy can enhance the treatment resistance of ovarian cancer cells, by progressively changing the cancer cell-intrinsic adhesion signalling and cell-surrounding microenvironment.
Intermediate magnification micrograph of a low malignant potential (LMP) mucinous ovarian tumour. H&E stain. Image credit: Nephron via Wikimedia, CC BY-SA 3.0
Platinum chemotherapy is a standard treatment in ovarian cancers, but treatment resistance commonly develops. The extracellular matrix (ECM)-derived biochemical and mechanical cues in the tumour microenvironment are known to contribute to the ability of cancer cells to metastasize and resist treatment. However, how the dynamic communication between the cancer cells and the ECM is affected by or influences the disease progression and chemotherapy, have remained elusive.
A new study led by Kaisa Lehti, a researcher at the Department of Microbiology, Tumor and Cell Biology at KI, and published in Nature Communications, shows that the ECM microenvironment is modulated in metastasis and following chemotherapy. Changes in the ECM proteins variably altered the cell death response of the tumour cells.
“Particularly in the most aggressive solid tumour tissues, cancer cells are surrounded by a prominent fibrotic network of proteins like collagens, known as the extracellular matrix (ECM) and also defined as the matrix some when considered with various associated factors including cytokines and chemokines. The ECM/matrix are produced largely by stromal cells but sensed and remodelled collectively by the cancer cells and the cells of the fibrotic tumour stroma. In tumour cells, specific ECM signalling in stiff microenvironment critically increased their resistance against platinum-mediated, apoptosis-inducing DNA damage”, Kaisa Lehti explains.
Source: Karolinska Institutet