Motility of select ovarian cancer cell lines: Effect of extracellular matrix proteins and the involvement of PAK2

Abstract

The interaction between tumor cells and extracellular matrix (ECM) proteins influences cell migration and the invasive behavior of cancer cells. In this study, we provide experimental evidence that collagen I and fibronectin affect ovarian cancer cell migration. In vitro wound healing assays and transwell migration assays were used to measure both total wound healing and directionality of individually migrating OV2008 and C13 ovarian cancer cells on glass, collagen I and fibronectin. Involvement of p21-activated kinase 2 (Pak2) in the motility of these cell lines was investigated using a chemical inhibitor as well as siRNA transfection. Culturing ovarian cancer cells on collagen type I (COLL) increased the migratory ability of OV2008 and C13 cells by increasing the directional migration of cells. In contrast, fibronectin (FN) decreased the migratory ability of OV2008 cells by reducing their ability to migrate directionally. When both cell lines are cultured on COLL and treated with increasing concentrations of a PAK inhibitor (IPA-3), there is a dose-dependent response such that there is a decrease in migration with an increase in inhibitor concentration. Further experiments utilizing PAK2 knockdown via siRNA transfection demonstrated significantly reduced migration of OV2008 cells on COLL as compared to those receiving control siRNA. In conclusion, our results indicate that FN and COLL affect the motility of the selected ovarian cancer cells lines and the effect of COLL is likely mediated, at least in part, by PAK2. A better understanding of the molecular events that contribute to tumor invasion and metastasis is crucial for developing novel treatment strategies to improve the long-term survival of women with ovarian cancer. As PAK2 is involved in motility, it should be further explored as a pro-metastatic gene in ovarian cancer.

Distinct molecular pathways in ovarian endometrioid adenocarcinoma with concurrent endometriosis

“…Although catenin beta 1 ( CTNNB1 ) was not a statistically significant change, it was downregulated in QPCR studies similar in direction to microarray results. P21 (RAC1) activated kinase 2 ( PAK2 ) has shown to decrease migration of ovarian cancer cells in vitro . PAK2 showed a 5.3‐fold downregulation in microarray analysis and 2.2‐fold change downregulation by QPCR ( p = 0.0009).…”

“…P21 (RAC1) activated kinase 2 (PAK2) has shown to decrease migration of ovarian cancer cells in vitro. 31 PAK2 showed a 5.3-fold downregulation in microarray analysis and 2.2-fold change downregulation by QPCR (p = 0.0009). The gene expression changes were validated by independent QPCR.…”

Peritoneal fluid stimulates neoplastic transformation of normal HEK 293 cells by high expression of pluripotent genes

“…Most ovarian cancers originate from the ovarian surface epithelium [18]. To improve the effectiveness of treatment of patients with ovarian cancer researchers should focus on understanding the molecular mechanism of invasiveness and metastasis [19]. The occurrence of metastasis causes a serious problem in relation to the cancer treatment.…”

Expansion of BCR/ABL1+ cells requires PAK2 but not PAK1

“…The latter concept is in line with the described roles of PAK1 and PAK2 in ECM remodelling: PAK1 enhances the expression of matrix metalloproteinase (MMP)1 and MMP3 in breast cancer cells and thereby supports the degradation of the extratumoural matrix (Rider et al , 2013). PAK2 increases the motility of ovarian cancer cells by enhancing breakdown of collagen type I (Flate & Stalvey, 2014). Our data support the latter concept because inhibitors for metalloproteinases ( TIMP1 , TIMP4 ) are increased upon knockdown of PAK2 .…”

“…The significance of PAK2 might be explained by its involvement in multiple pathways with the potential to drive ECM remodelling and motility of cancer cells, including those featuring cytoskeletal effector proteins (Misra et al , 2005; Kumar et al , 2006; Chen et al , 2009; Flate & Stalvey, 2014; Radu et al , 2014). …”