Neuropilin‐1 is differentially expressed in myoepithelial cells and vascular smooth muscle cells in preneoplastic and neoplastic human breast: A possible marker for the progression of breast cancer

Stephenson, John M.; Banerjee, Snigdha; Saxena, Neela K.; Cherian, Rachel; Banerjee, Sushanta K.

doi:10.1002/ijc.10611

Cited by 109 publications

(81 citation statements)

References 37 publications

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“…The NRP-1 is a transmembrane receptor glycoprotein whose expression is known to be increased during the progression of breast, prostate, and lung tumors (Soker et al, 1998;Stephenson et al, 2002;Lantuejoul et al, 2003;Vanveldhuizen et al, 2003). The NRP-1 serves as a vascular endothelial growth factor (VEGF) coreceptor and enhances VEGF receptor 2 (VEGFR2)/kinase insert domain-containing receptor (KDR) binding, tumor angiogenesis, and progression (Soker et al, 1998;Miao et al, 2000).…”

Section: Discussionsupporting

confidence: 45%

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Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro

et al. 2004

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In the present study, we showed that a single-dose treatment of normal breast epithelial cell line, MCF10A, for 72 h with cigarette smoke condensate (CSC) resulted in a transformed phenotype. The anchorage-dependent growth of these cells was decreased due to increased cell cycle arrest in S-G 2 /M phase; however, the surviving cells developed resistance due to an increased Bcl-xL to Bax ratio. Levels of PCNA and gadd45 proteins -involved in DNA repair in response to genomic damage -were increased, suggesting that the cells were responding to CSC-induced genomic damage. The transformation of MCF10A cells was determined by their colony-forming efficiency in soft-agar in an anchorage-independent manner. CSC-treated MCF10A cells efficiently formed colonies in soft-agar. We then re-established cell lines from the soft-agar colonies and further examined the persistence of their transforming characteristics. The reestablished cell lines, when plated after 17 passages without CSC treatment, still formed colonies in the softagar. An increased staining of neuropilin-1 (NRP-1) further showed a transformation characteristic of MCF10A cells treated with CSC. In summary, our results suggest that CSC is capable of transforming the MCF10A cells in vitro, supporting the role of cigarette smoking and increased risk for breast cancer.

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Section: Discussionsupporting

confidence: 45%

“…The expression of NRP-1 has been suggested as one of the markers for the neoplastic progression of breast cancer cells (Soker et al, 1998;Stephenson et al, 2002). In the present study, we hypothesized that if CSC (Figure 7).…”

Section: Selective Growth Of Mcf10a Cells After Treatment With Cscsupporting

confidence: 39%

Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro

et al. 2004

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“…Neuropilins are widely expressed in normal mature and developing vasculature both on vascular smooth muscle cells (11,83) and endothelial cells (50). Their presence has also been detected in tumor vascular endothelium (10 -13), an important finding with regard to their role in promoting pathologic angiogenesis in malignancy.…”

Section: Role Of Neuropilin In Angiogenesis Expressionsupporting

confidence: 44%

The role of neuropilins in cancer

Ellis

2006

Molecular Cancer Therapeutics

231

194

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Neuropilins are multifunctional non -tyrosine kinase receptors that bind to class 3 semaphorins and vascular endothelial growth factor. NRP-1 and NRP-2 were first identified for their key role in mediating axonal guidance in the developing nervous system through their interactions with class 3 semaphorins. Growing evidence supports a critical role for these receptors in tumor progression. Neuropilin expression is up-regulated in multiple tumor types, and correlates with tumor progression and prognosis in specific tumors. Neuropilins may indirectly mediate effects on tumor progression by affecting angiogenesis or directly through effects on tumor cells. This article reviews emerging evidence for the role of neuropilins in tumor biology. The therapeutic implications of these data are far-reaching and suggest that neuropilin-targeted interventions may be useful as a component of antineoplastic therapy.

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“…Although expression of the neuropilins was originally thought to be limited to neurons, these receptors have since been identified on inflammatory cells (16), vascular smooth muscle cells (17), endothelial cells (13,18), and, most recently, tumor cells (reviewed in ref. 10).…”

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confidence: 43%

Neuropilin-2–Mediated Tumor Growth and Angiogenesis in Pancreatic Adenocarcinoma

Dallas

Gray

Xia³

et al. 2008

Clinical Cancer Research

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Purpose. Neuropilin-2 (NRP-2) is a coreceptor for vascular endothelial growth factor (VEGF) on endothelial cells. NRP-2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) cells relative to nonmalignant ductal epithelium.This study determined the role of NRP-2 in PDAC cells. Experimental Design. NRP-2 expression was reduced in PDAC cells with stable short-hairpin RNA (shRNA) transfection. Western blotting was done to evaluate signaling intermediates. Migration and invasion studies were carried out in Boyden chambers. Anchorage-independent growth was assessed by soft-agar colony formation. In vivo growth was evaluated using murine subcutaneous and orthotopic xenograft models. Immunohistochemical analysis evaluated in vivo proliferation and angiogenesis. Results. shRNA-NRP-2 decreased NRP-2 levels without affecting neuropilin-1 levels. Akt activation was decreased in clones with reduced NRP-2 (shRNA-NRP-2). shRNA-NRP-2 cells showed decreased migration, invasion, and anchorage-independent growth compared with control cells. In vitro proliferation rates were similar in control-and shRNA-transfected cells. Subcutaneous and orthotopic xenografts from shRNA-transfected cells were significantly smaller than those resulting from control-transfected cells (P < 0.05). Furthermore, shRNA-NRP-2 tumors exhibited less cellular proliferation and decreased microvascular area relative to control tumors (P < 0.05). Constitutive expression of the angiogenic mediator Jagged-1 was reduced in shRNA-NRP-2 cells, whereas vascular endothelial growth factor levels were unchanged. Conclusion. Reduction of NRP-2 expression in PDAC cells decreased survival signaling, migration, invasion, and ability to grow under anchorage-independent conditions. In vivo, reduction of NRP-2 led to decreased growth of xenograft tumors and decreased vascular area, which was associated with decreased Jagged-1levels. NRP-2 is a potential therapeutic target on PDAC cells.

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Neuropilin‐1 is differentially expressed in myoepithelial cells and vascular smooth muscle cells in preneoplastic and neoplastic human breast: A possible marker for the progression of breast cancer

Cited by 109 publications

References 37 publications

Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro

Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro

The role of neuropilins in cancer

Neuropilin-2–Mediated Tumor Growth and Angiogenesis in Pancreatic Adenocarcinoma

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