In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors

Abstract

Abstract. Matrix metalloproteinases (MMPs) secreted by cervical and ovarian cancer, especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 expression in cervical and ovarian cancer cell lines. Human cervical (HeLa and DoTc2-4510) and ovarian (SK-OV-3) cell lines were cultured in appropriate media. At near confluence, the cells were washed with PBS and incubated in serum-free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. HeLa and SK-OV-3 cell lines expressed MMP-2 whereas DoTc2-4510 cells expressed MMP-9. Treatment of cervical cancer cell lines (HeLa and DoTc2-4510) with PMA had no effect on MMP-2 expression and a moderate stimulatory effect in ovarian cancer cell line SK-OV-3. MMP-9 was stimulated by phorbol 12-myristate 13-acetate in HeLa cells and enhanced in DoTc2-4510. Tumor necrosis factor-· and interleukin-1ß, had slight inhibitory effect on HeLa cell expression of MMP-2 while lipopolysaccharide stimulated MMP-2 in HeLa cells. Doxycycline, epigallocatechin gallate, a nutrient mixture, actinomycin-D, cyclohexamide, retinoic acid and dexamethasone inhibited MMP-2 in HeLa and SK-OV-3 cell lines and inhibited MMP-9 in DoTc2-4510. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in ovarian and cervical cancer cell lines, suggesting these agents may be effective strategies to treat these cancers.

Glycoprotein nonmetastatic melanoma protein B accelerates tumorigenesis of cervical cancer in vitro by regulating the Wnt/β-catenin pathway

“…In cervical cancer, dysregulation of MMP-2 and MMP-9 has been widely reported. MMP-2 and MMP-9 expression and activation can be affected by various factors, including cytokines, mitogens, inducers, inhibitors, E6/E7 oncoproteins of human papillomavirus 16 (HPV16), and others (22,23). It was reported that the activation of MMP-2 in cervical cancer tissue could be mediated by a functional complex consisting of α(v)β3 integrin/membrane type-1 metalloproteinase-2 (MT1-MMP)/tissue inhibitor of metalloproteinase-2 (TIMP-2) on tumor cell surface (24).…”

Platelet-Membrane-Camouflaged Zirconia Nanoparticles Inhibit the Invasion and Metastasis of Hela Cells

“…Matrix metallopeptidases (MMPs) degrade the extracellular matrix and basement membrane (Lengyel et al, 2001), enhancing the spread of cancer cells to distant sites (Shen et al, 2017). MMP2 and MMP9 degrade collagen IV in the extracellular basement membrane (Roomi et al, 2010) and rearrange the extracellular matrix during invasion and migration of cancer cells (Nabeshima et al, 2002;Alaseem et al, 2019). Moreover, active level of MMP2 in cancer cells is related to invasion and metastasis (Celentano et al, 2020).…”

The Relationship Between MMP-2 -1306C>T and MMP-9 -1562C>T Polymorphisms and the Risk and Prognosis of T-Cell Acute Lymphoblastic Leukemia in a Chinese Population: A Case-Control Study

“…Among them, MMP-2 and MMP-9 belong to the zinc ion-dependent endopeptidases are found in a wide variety of tissues [10‒12]. MMP-2 and MMP -9 expressions have been correlated with cell invasion and tumor size in several cancers such as lung cancer, breast cancer, cervical cancer and ovarian cancer [13‒15]. MMP-2 and MMP-9 have also been strongly connected with extramedullary infiltrates in adult acute lymphoblastic leukemia (ALL) [16].…”