Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells

Smith, Paul; Rhodes, Nicholas P.; Shortland, Adam P; Fraser, Scott P.; Djamgoz, Mustafa B.A.; Ke, Youqiang; Foster, Christopher S.

doi:10.1016/s0014-5793(98)00050-7

Cited by 96 publications

(85 citation statements)

References 19 publications

(27 reference statements)

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“…Previous invasion assays have demonstrated the benign nature of PNT-2 cells and the progressively malignant characteristics of LNCaP, Du-145 and PC-3, in terms of their ability invade basement membranes in vitro. 30,31 Western blot also detected nearly a 6-fold of increment of OPN expression in the highly malignant tissues when compared with those expressed in the normal and BPH samples (Fig. 2).…”

Section: Discussionmentioning

confidence: 78%

Prognostic significance of osteopontin expression in human prostate cancer

Forootan

Foster

Aachi

et al. 2005

Intl Journal of Cancer

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To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT-2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du-145 and PC-3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 6 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6-fold to 5.9 6 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (1). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (1) and 4 (11%) were unstained (2). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (111), 20 (29%) stained moderately positive (11) and 19 (27%) stained weakly positive (1). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p 5 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi-square test, p < 0.0001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly (n 5 70, p 5 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi-square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival. ' 2005 Wiley-Liss, Inc.Key words: prostate carcinoma; osteopontin; benign prostate hyperplasia (BPH); Gleason scores; patient survival Prostate cancer has become the most common male cancer and the second leading cause of death from male malignant disease in the United States and Europe, and this disease kills more than 40,000 men per year in the developed world. 1,2 Despite the increasing incidence, the molecular basis of prostate cancer progression, invasion and metastasis is still not fully understood. The complicated molecular pathology of prostate cancer may involve a series of sequential genetic events, which cause the initiation and progression of the malignant changes of prostate epithelial cells. The complicated genetic events responsible for tumorigenicity and metastasis of prostate cancer may be classified in a simple ...

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Section: Discussionmentioning

confidence: 78%

Prognostic significance of osteopontin expression in human prostate cancer

Forootan

Foster

Aachi

et al. 2005

Intl Journal of Cancer

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“…Ion channels regulate, and stimulate numerous behavioral changes in cells that are associated with cancer and metastasis, including cell movement (elongation and lateral motility) (4,5), migration, galvanotaxis (6) and invasion (7,8). A number of in vitro (9)(10)(11) and in vivo (12) studies performed using tetrodotoxin (TTX), which specifically blocks voltage-gated sodium channels (VGSCs) (13), have suggested that the plasma membrane of prostate cancer cells may gain a more excitable phenotype due to increased VGSC expression, and thus malignancy is able to progress. Bennett et al (11) demonstrated that VGSC expression was 'necessary' and 'enough' for the invasiveness of prostate cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Effects of Hedera helix L. extracts on rat prostate cancer cell proliferation and motility

Aktaş

Altun

2016

Oncology Letters

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Abstract. Hedera helix L., a member of Araliaceae family, has antiproliferative, cytotoxic, antimicrobial, antifungal, antiprotozoal and anti-inflammatory effects, and is used in cosmetics. The aim of the present study was to investigate the effect of treatment with extracts of leaves and unripened fruits of H. helix on rat prostate cancer cell lines with markedly different metastatic potentials: Mat-LyLu cells (strongly metastatic) and AT-2 cells (weakly metastatic). The effects of the extracts on cell kinetics and migration were determined. Tetrodotoxin was used to block the voltage-gated sodium channels (VGSCs) associated specifically with Mat-LyLu cells. Cell proliferation was detected spectrophotometrically using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The mitotic index was determined using the Feulgen staining method. Lateral motility was quantified by wound-healing assays. The results of the present study demonstrated that cell kinetics (proliferation and mitotic activity) and motility were inhibited by ethanolic leaf extract of H. helix. The ethanolic extract of H. helix fruit suppressed Mat-LyLu cell migration, with no effect on proliferation. The opposite effects were observed in AT-2 cells; migration was not affected but proliferation was inhibited. In conclusion, the ethanolic fruit extract of H. helix may inhibit the cell migration of Mat-LyLu cells by blocking VGSCs. However, the effect of ethanolic leaf extract of H. helix treatment on the lateral motility of the cancer cells is unclear. IntroductionProstate cancer is the second most common cause of cancer-associated mortality among men worldwide (1). By the time prostate cancer is diagnosed, metastasis has occurred in the majority of men, as early prostate cancer has no symptoms. Metastatic diseases are a significant public health problem affecting cancer patients and their families (2). Metastasis occurs when malignant cells leave the primary tumor, migrate via the circulatory system, localize in distant areas and lead to the development of secondary tumors. It is a multistep process, and the steps are similar in all tumors. Mobilization of tumor cells is an important step in metastasis (3). Ion channels regulate, and stimulate numerous behavioral changes in cells that are associated with cancer and metastasis, including cell movement (elongation and lateral motility) (4,5), migration, galvanotaxis (6) and invasion (7,8). A number of in vitro (9-11) and in vivo (12) studies performed using tetrodotoxin (TTX), which specifically blocks voltage-gated sodium channels (VGSCs) (13), have suggested that the plasma membrane of prostate cancer cells may gain a more excitable phenotype due to increased VGSC expression, and thus malignancy is able to progress. Bennett et al (11) demonstrated that VGSC expression was 'necessary' and 'enough' for the invasiveness of prostate cancer cells. Prostate cancer tends to invade the bones, lungs and lymph nodes (14). Combating metastasis formation and growth are important for succ...

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“…[10][11][12] Furthermore, VGSC activity could directly enhance metastatic ability by potentiating essential cellular behaviours integral to the metastatic cascade, including process extension, 13 adhesion, lateral motility, 15 directional movement in a small directcurrent electric field (galvanotaxis), 16,17 secretory membrane activity 18 and transverse invasion. [10][11][12] A more recent study has shown that overexpression of VGSC alone is sufficient to increase the invasive potential of nonmetastatic and moderately metastatic human CaP cells in vitro. 19 These results raised the possibility that VGSC expression could be a novel marker of cancer and metastatic potential in human CaP.…”

Section: Introductionmentioning

confidence: 99%