Reduced expression of actin-binding proteins, h-caldesmon and calponin h1, in the vascular smooth muscle inside melanoma lesions: an adverse prognostic factor for malignant melanoma

Koganehira, Yoko; Takeoka, Michiko; Ehara, Takashi; Sasaki, Katsunori; Murata, Hiroshi; Saida, Toshiaki; Taniguchi, Shun’ichiro

doi:10.1046/j.1365-2133.2003.05238.x

Cited by 30 publications

(26 citation statements)

References 28 publications

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“…Interestingly, out of a 17-gene signature recently found to associate with metastatic propensity in various types of human solid tumors (32), 4 of 9 downregulated genes (actin γ2, myosin light chain kinase, myosin heavy chain 11, and calponin h1) are markers of SMCs. Another study provided a similar negative correlation between the expression of the SMC marker h-caldesmon and metastasis in human melanoma (35). SMC contribution to a solid tumor is mainly in the form of VSMCs/pericytes.…”

Section: Discussionmentioning

confidence: 59%

Pericytes limit tumor cell metastasis

Xian¹

2006

Journal of Clinical Investigation

302

226

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Previously we observed that neural cell adhesion molecule (NCAM) deficiency in β tumor cells facilitates metastasis into distant organs and local lymph nodes. Here, we show that NCAM-deficient β cell tumors grew leaky blood vessels with perturbed pericyte-endothelial cell-cell interactions and deficient perivascular deposition of ECM components. Conversely, tumor cell expression of NCAM in a fibrosarcoma model (T241) improved pericyte recruitment and increased perivascular deposition of ECM molecules. Together, these findings suggest that NCAM may limit tumor cell metastasis by stabilizing the microvessel wall. To directly address whether pericyte dysfunction increases the metastatic potential of solid tumors, we studied β cell tumorigenesis in primary pericyte-deficient Pdgfb ret/ret mice. This resulted in β tumor cell metastases in distant organs and local lymph nodes, demonstrating a role for pericytes in limiting tumor cell metastasis. These data support a new model for how tumor cells trigger metastasis by perturbing pericyte-endothelial cell-cell interactions.

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Section: Discussionmentioning

confidence: 59%

Pericytes limit tumor cell metastasis

Xian¹

2006

Journal of Clinical Investigation

302

226

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“…We and others (14,24,39) have recently shown that caldesmon negatively regulates the formation of podosomes and rosettes by vascular smooth muscle cells (SMC) transformed with Src. Caldesmon expression is downregulated in transformed cells and cancer cells (43,47,49) and is inversely correlated with metastatic frequency in malignant melanoma (30). In addition, caldesmon is implicated in the suppression of cancer cell invasion (57).…”

mentioning

confidence: 99%

p53 Suppresses Src-Induced Podosome and Rosette Formation and Cellular Invasiveness through the Upregulation of Caldesmon

Mukhopadhyay

Eves

Jia

et al. 2009

Molecular and Cellular Biology

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The tumor-suppressive role of p53 at the level of tumor initiation is well documented. It has also been shown previously that p53 acts against tumor progression/metastasis. However, its role in modulating cell migration and invasion leading to metastasis is poorly understood. In this study, using vascular smooth muscle cells and NIH 3T3 fibroblast cells, we have shown that p53 potently suppresses Src-induced podosome/rosette formation, extracellular matrix digestion, cell migration, and invasion. The overexpression of exogenous wild-type p53 or the activation of the endogenous p53 function suppresses, while the short hairpin RNA-mediated knockdown of p53 expression or the blocking of its function exacerbates, Src-induced migratory and invasive phenotypes. We have also found that p53 expression and function are downregulated in cells stably transformed with constitutively active Src that exhibit aggressive invasive properties. Lastly, p53 upregulates the expression of caldesmon, an actin-binding protein that has been shown to be an inhibitor of podosome/invadopodium formation. The ability of p53 to suppress Src phenotypes in transformed cells was largely abolished by knocking down caldesmon. This study reports a novel molecular mechanism (caldesmon), as well as a structural basis (podosomes/rosettes), to show how p53 can act as an anti-motility/invasion/metastasis agent.

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“…Calpronin and caldesom are regulatory proteins, which function in the induction of actin polymerization and depolymeriztion, and maintain cytoskeletal stability during hypertrophy (el-Mezgueldi, 1996;Huber, 1997), while caldesom prevents actin reorganization (Castellino et al, 1995). In this study, calponin and caldesom expression were enhanced in both infected microglia and astrocytes and have been shown to block actin reorganization, induce actin aggregation, and destabilize cytoskeletal integrity (Winder et al, 1993;Lu et al, 1995;Koganehira et al, 2003;Takiguchi and Matsumura, 2005;Perez-Montiel et al, 2006). Additionally, interaction of HIV-infected astrocytes markedly enhanced expression of structural proteins, vimentin and GFAP, by HIV-1 infected microglia, which have been shown to inhibit neurotrophin secretion (Schwartz and Mishler, 1990) and down-regulate production of TNF-〈 (Hetier et al, 1991).…”

Section: Discussionmentioning

confidence: 74%

HIV-1-Infected Astrocytes and the Microglial Proteome

Wang

Gong

Liu

et al. 2008

J Neuroimmune Pharmacol

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The human immunodeficiency virus (HIV) invades the central nervous system early after viral exposure but causes progressive cognitive, behavior, and motor impairments years later with the onset of immune deficiency. Although in the brain, HIV preferentially replicates productively in cells of mononuclear phagocyte (MP; blood borne macrophage and microglia), astrocytes also can be infected, at low and variable frequency, particularly in patients with encephalitis. Among their many functions, astrocytes network with microglia to provide the first line of defense against microbial infection; however, very little is known about its consequences on MP. Here, we addressed this question using co-culture systems of HIV infected mouse astrocytes and microglia. Pseudotyped vesicular stomatis virus/HIV was used to circumvent absence of viral receptors and ensure cell genotypic uniformity for studies of intercellular communication. The study demonstrated that infected astrocytes show modest changes in protein elements as compared to uninfected cells. In contrast, infected astrocytes induce robust changes in the proteome of HIV-1 infected microglia. Accelerated cell death and redox proteins, amongst others, were produced in abundance. The observations confirmed the potential of astrocytes to influence the neuropathogenesis of HIV-1 infection by specifically altering the neurotoxic potential of infected microglia and in this manner, disease progression.

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Reduced expression of actin-binding proteins, h-caldesmon and calponin h1, in the vascular smooth muscle inside melanoma lesions: an adverse prognostic factor for malignant melanoma

Cited by 30 publications

References 28 publications

Pericytes limit tumor cell metastasis

Pericytes limit tumor cell metastasis

p53 Suppresses Src-Induced Podosome and Rosette Formation and Cellular Invasiveness through the Upregulation of Caldesmon

HIV-1-Infected Astrocytes and the Microglial Proteome

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