Evidence shows that manipulation of the extracellular matrix (ECM), a major component of a tumor’s microenvironment, can have suppressive effects on various cancers, including breast, urinary bladder, and prostate cancers. According to the tissue organization field theory, manipulating tumor microenvironments can impact the survival of cancer cells. However, this theory has not yet been tested in glioblastoma multiforme, an aggressive cancer with a poor prognosis for patients.
In a recent publication in Oncotarget, M. H. Murdock et al. investigated the in vitro and in vivo effects of a saline-soluble fraction of non-neoplastic ECM harvested from porcine urinary bladder (ECM-SF) on glioma cells. ECM-SF, which is easily acquired and FDA-approved for clinical applications, was shown to induce apoptosis in glioma cells in vitro. Apoptosis in glioma cells was confirmed using NucView® 488, which showed increasing amounts of nuclear fluorescence over 12 hours of ECM-SF treatment in primary glioma cells (designated 0319 and 1119 in the figure below) compared to non-neoplastic HMC3 CNS cells. Intratumoral injections of ECM-SF into glioma tumors were shown to decrease tumor volume in vivo and correlated with increased median survival from 24.5 to 51 days in rats.
These results support the hypothesis that ECM and resident cells can influence each other through bidirectional crosstalk. This is thought to be a mechanism by which non-neoplastic cells can be influenced by cancer cells to express cancer-like properties. Likewise, cancer cells could be influenced by non-neoplastic environments to become less cancer-like. Further research on the anti-cancer effects of the ECM is needed to determine a possible role for it in cancer therapy.
Murdock, M. H., Hussey, G. S., Chang, J. T., Hill, R. C., Nascari, D. G., Rao, A. V., Hansen, K. C., Foley, L. M., Hitchens, T. K., Amankulor, N. M., & Badylak, S. F. (2022). A liquid fraction of extracellular matrix inhibits glioma cell viability in vitro and in vivo. Oncotarget, 13, 426–438. https://doi.org/10.18632/oncotarget.28203