Dual roles of tumour cells-derived matrix metalloproteinase 2 on brain tumour growth and invasion

Abstract

Background:A previous study on a murine astrocytoma cell-line ALTS1C1 showed a highly invasive pattern similar to clinical anaplastic astrocytoma in vivo. This cell-line also expressed a high level of matrix metalloproteinase 2 (MMP2). This study aimed to verify the role of MMP2 in brain tumour progression.Methods:ALTS1C1 and MMP2 knockdown (MMP2kd) cells were inoculated intracranially, and tumour microenvironment was assessed by immunohistochemistry staining.Results:MMP2 expression was co-localised with CD31-positive cells at invading the tumour front and correlated with an invasive marker GLUT-1. The suppression of MMP2 expression prolonged the survival of tumour-bearing mice associated with tumours having smoother tumour margins, decreased Ki67-proliferating index, and down-regulated GLUT-1 antigen. Although the reduction of MMP2 expression did not alter the vessel density in comparison to parental ALTS1C1 tumours, vessels in MMP2kd tumours were less functional, as evidenced by the low ratio of pericyte coverage and reduction in Hoechst33342 dye perfusion.Conclusions:This study illustrated that tumour-derived MMP2 has at least two roles in tumour malignancy; to enhance tumour invasiveness by degrading the extracellular matrix and to enhance tumour growth by promoting vessel maturation and function.

The Activity of Matrix Metalloproteinases (MMP-2, MMP-9) and Their Tissue Inhibitors (TIMP-1, TIMP- 3) in the Cerebral Cortex and Hippocampus in Experimental Acanthamoebiasis

“…MMP-2 is constitutively expressed by several cell types including brain tissue, and participates in BBB damage and immunological pathogenesis [12]. In addition, it plays a role in the growth, infiltration and formation of cancer metastases [21]. Similar to monocytes, T-cells, astrocytes, microglia, and macrophages, neutrophils flow to damaged tissues and release large amounts of MMP-9 from their granules [14,22].…”

Genetic, epigenetic and transcriptional comparison of esophagus tumor‑associated and adjacent normal myofibroblasts

“…3A). Since the secreted gelatinase MMP2 localizes on the surface of the migrating cells (23) and accumulates mainly on the leading edge of invasive tumors (24), in-gel zymography was used to test gelatinolytic activity in MF cell lysates and conditioned cell media. Although zymograms indicated no significant differences in MMP2 activities between cell lysates of esophageal tumor-derived and normal tissue MFs, conditioned media of the tumor-associated cells exhibited markedly higher MMP2 activity compared with the medium of normal MFs (Fig.…”

Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural Insights from a Computational Model

“…well-known [55,80]. MMP2, for instance, can not only induce tumor cell invasion by degrading ECM but promote tumor cell proliferation by enhancing vessel maturation and function in brain tumors [80].…”

“…well-known [55,80]. MMP2, for instance, can not only induce tumor cell invasion by degrading ECM but promote tumor cell proliferation by enhancing vessel maturation and function in brain tumors [80]. In particular, inhibition of MMP activity can block cancer cell invasion by suppressing cell-ECM tractions and inducing cell softening [55].…”