Calponin h1 induced a flattened morphology and suppressed the growth of human fibrosarcoma HT1080 cells

Takeoka, Michiko; Ehara, Takashi; Sagara, Junji; Hashimoto, Shingo; Taniguchi, Shun’ichiro

doi:10.1016/s0959-8049(01)00390-2

Cited by 31 publications

(38 citation statements)

References 24 publications

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“…However, CNh1 gene transfection into the peritoneal cells of knockout mice could successfully inhibit cancer cell invasion into peritoneal cell layer (14,15). The efficacy of CNh1 transfection into cancer cells themselves was also reported by our colleagues; both cell growth and tumorigenicity were significantly inhibited in CNh1-transfected leiomyosarcoma cells (16) and fibrosarcoma cells (17).…”

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confidence: 53%

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Adenovirus-Mediated Calponin h1 Gene Therapy Directed against Peritoneal Dissemination of Ovarian Cancer: Bifunctional Therapeutic Effects on Peritoneal Cell Layer and Cancer Cells

Ogura

Kobayashi

Ueoka

et al. 2006

Clinical Cancer Research

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Purpose: Calponin h1 (CNh1), one of the family of actin-binding proteins, stabilizes the filaments of actin and modulates various cellular biological phenotypes. Recent studies revealed the close correlation between the invasive tumor spread and the reduced expression of CNh1 and α-smooth muscle actin in the surrounding stromal cells. The purpose of this study is to evaluate the efficacy of i.p. CNh1 gene therapy against peritoneal dissemination of ovarian cancer. Experimental Design: We used an adenoviral vector to induce the CNh1 gene into peritoneal cells and ovarian cancer cells as a means of enhancing or inducing the expression of α-smooth muscle actin as well as CNh1. The efficacy of gene transfer was examined by in vitro cell culture and in vivo animal experiments. Results: The formation of longer and thicker actin fibers was observed in each transfected cell line, and the localization of these fibers coincided with that of externally transducted CNh1. With respect to changes in cell behavior, the CNh1-transfected peritoneal cells acquired an ability to resist ovarian cancer-induced shrinkage in cell shape; thus, cancer cell invasion through the monolayer of peritoneal cells was inhibited. In addition, CNh1-transfected ovarian cancer cells showed suppressed anchorage-independent growth and invasiveness, the latter of which accompanied impaired cell motility. The concomitant CNh1 transfection into both peritoneal cells and ovarian cancer cells produced an additive inhibitory effect with respect to cancer cell invasion through the peritoneal cell monolayer. By in vivo experiments designed to treat nude mice that had been i.p. inoculated with ovarian cancer cells, we found that the i.p. injected CNh1 adenovirus successfully blocked cancer-induced morphologic changes in peritoneal cell surface and significantly prolonged the survival time of tumor-bearing mice. Moreover, CNh1 adenovirus could successfully enhance the therapeutic effect of an anticancer drug without increase in side effects. Conclusions: Thus, CNh1 gene therapy against peritoneal dissemination of ovarian cancer is bifunctionally effective (i.e., through inhibitory effects on the infected peritoneal cell layers that suppress cancer invasion and through direct antitumor effects against invasion and growth properties of cancer cells).

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confidence: 53%

“…A human CNh1 cDNA was subcloned into a pCMV-neo-Bam vector as described previously (17). Either CNh1 cDNA construct or control vector (20 Ag) was transfected into SKOV3 cell line by Lipofectin method.…”

Section: Methodsmentioning

confidence: 99%

Adenovirus-Mediated Calponin h1 Gene Therapy Directed against Peritoneal Dissemination of Ovarian Cancer: Bifunctional Therapeutic Effects on Peritoneal Cell Layer and Cancer Cells

Ogura

Kobayashi

Ueoka

et al. 2006

Clinical Cancer Research

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“…High levels of expression for the actin-binding protein h1CaP are known to be required for the maintenance of a normal smooth muscle phenotype (Horiuchi et al, 1998;Horiuchi et al, 1999;Meehan et al, 2002). Downregulation of h1CaP, in contrast, is generally accompanied with smooth muscle dedifferentiation (Gimona et al, 1990;Horiuchi et al, 1999) and malignant alterations of smooth muscle tissue (Takeoka et al, 2002). The molecular mechanism underlying the increased tumor forming potential of CaP-deficient cells remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Podosome formation in cultured A7r5 vascular smooth muscle cells requires Arp2/3-dependent de-novo actin polymerization at discrete microdomains

Kaverina

Stradal

Gimona

2003

Journal of Cell Science

129

122

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Phorbol ester triggers the conversion of focal adhesions into podosomes in A7r5 smooth muscle cells. Here we followed the dynamics of podosome formation using dual fluorescence live video and confocal microscopy, as well as interference reflection and evanescent wave microscopy. We show that podosomes form at the outer region of stress fiber bundles, at specialized sites where they are embedded in adhesion plaques at the basal surface of the plasma membrane, and that cortactin resides constitutively at these microdomains. We further demonstrate that the formation of podosomes requires Arp2/3-dependent actin polymerization at the stress fiber-focal adhesion interface. Concentration of Arp2/3 coincides with podosome formation and precedes the engagement of SM22 and alpha-actinin, while the focal adhesion components zyxin and vinculin redistribute only at later stages of podosome development. We thus suggest that the genesis of podosomes includes two steps, one requiring the early de novo polymerization of actin filaments, and a second, late phase characterized by the recruitment of focal adhesion components. Moreover, we provide evidence for the existence of an as yet unidentified region in close proximity to the focal adhesion-stress fiber interface, which marks the site of actin cytoskeleton remodeling and is a novel site of Arp2/3-dependent F-actin polymerization.Movies available online

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“…8) Previous studies revealed that CNh1 gene transfection into fibroblast, leiomyosarcoma, and fibrosarcoma cell lines resulted in a reduction of cell proliferation or tumor growth. 6,7,10) However, the mechanism of the tumor-suppressive effect of CNh1 remains to be determined. In the present study, we transfected human CNh1 cDNA into an src-transformed fibroblastic cell line SR-3Y1 and showed that CNh1 suppressed the tumor growth in association with a decrease in VEGF expression and angiogenesis and also in part with a reduction in cell proliferative potential and cell motility.…”

Section: Discussionmentioning

confidence: 99%

“…5,6) Further, we obtained similar results in a fibrosarcoma cell line, HT1080. 7) Various studies have suggested that CNh1 is associated with suppression of malignant or metastatic phenotypes, [8][9][10][11] but the mechanism is not fully clarified. In the present study, we transfected the human CNh1 gene into a src-induced transformed fibroblast cell line, SR-3Y1, where the causative gene for the transformation was clearly defined, to investigate the effect of CNh1 on the cell proliferation, motility and tumor growth.…”

mentioning

confidence: 99%

Calponin h1 Suppresses Tumor Growth of Src‐induced Transformed 3Y1 Cells in Association with a Decrease in Angiogenesis

Kaneko

Takeoka

Oguchi

et al. 2002

Japanese Journal of Cancer Research

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Calponin h1 (CNh1) is a basic actin-binding protein that is abundantly expressed in smooth muscle cells and involved in smooth muscle contraction by inhibiting actomyosin MgATPase. In recent studies, CNh1 was noted to suppress cell proliferation and tumorigenicity in leiomyosarcoma and tumor growth in fibrosarcoma cell lines. To further investigate the function of CNh1 as a tumor suppressor, we transfected the human CNh1 gene into a v-src-transformed rat fibroblast cell line SR-3Y1. The volume of the tumors derived from one randomly selected CNh1-transfectant (C1) in nude mice was reduced to 34.1% of that from a randomly selected vector transfectant (V1). A similar tendency was observed in another independent pair (C2, V2). Pathological analysis showed a significant decrease in the number of mitotic cells in the CNh1-transfectants. Further, a marked reduction in the number of vessels in the CNh1-transfectant was observed. DNA synthesis under conditions without serum was significantly reduced in the CNh1-transfectant (C1) compared with the control transfectant (V1), while no significant difference was seen in the cellular growth in the presence of 10% serum. A slight but significant reduction in in vitro cellular motility in the CNh1-transfectant was also observed. While the suppression of growth potential and cell motility by CNh1 transfer was significant but partial, a marked reduction in vascular endothelial growth factor (VEGF) mRNA and the secretion of VEGF protein was observed in the CNh1-transfectant. These results suggest that CNh1 plays a role as tumor suppressor in SR-3Y1 mainly by decreasing VEGF expression and angiogenesis in vivo and partially through reducing cellular proliferative potential and cell motility.

show abstract

Calponin h1 induced a flattened morphology and suppressed the growth of human fibrosarcoma HT1080 cells

Cited by 31 publications

References 24 publications

Adenovirus-Mediated Calponin h1 Gene Therapy Directed against Peritoneal Dissemination of Ovarian Cancer: Bifunctional Therapeutic Effects on Peritoneal Cell Layer and Cancer Cells

Adenovirus-Mediated Calponin h1 Gene Therapy Directed against Peritoneal Dissemination of Ovarian Cancer: Bifunctional Therapeutic Effects on Peritoneal Cell Layer and Cancer Cells

Podosome formation in cultured A7r5 vascular smooth muscle cells requires Arp2/3-dependent de-novo actin polymerization at discrete microdomains

Calponin h1 Suppresses Tumor Growth of Src‐induced Transformed 3Y1 Cells in Association with a Decrease in Angiogenesis

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