NRP1-positive lung cancer cells possess tumor-initiating properties

Jimenez-Hernandez, Luis Enrique; Vázquez-Santillán, Karla; Castro-Oropeza, Rosario; Martínez-Ruiz, Gustavo Ulises; Muñoz-Galindo, Laura; González-Torres, Carolina; Cortés-González, Carlo César; Victoria-Acosta, Georgina; Meléndez-Zajgla, Jorge; Maldonado, Vilma

doi:10.3892/or.2017.6089

Cited by 29 publications

(31 citation statements)

References 37 publications

(41 reference statements)

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“…The transcription factor MYC is overexpressed in many cancers and regulates the expression of multiple genes involved in the determination of cancer cell fate. Neuropilin-1 is a transmembrane protein also overexpressed in many tumors displaying growth-promoting functions and mediates tumor-initiating properties [49]. The disulfide isomerase PDIA6 has been shown to enable shedding of tumor-associated NKG2D (natural killer group 2, member D) ligands that promote resistance to cancer, thus contributing to tumor immune escape [50].…”

Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Fellenberg

Lehner

Saehr

et al. 2019

Cancers

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Since the introduction of high-dose chemotherapy about 35 years ago, survival rates of osteosarcoma patients have not been significantly improved. New therapeutic strategies replacing or complementing conventional chemotherapy are therefore urgently required. MicroRNAs represent promising targets for such new therapies, as they are involved in the pathology of multiple types of cancer, and aberrant expression of several miRNAs has already been shown in osteosarcoma. In this study, we identified silencing of miR-127-3p and miR-376a-3p in osteosarcoma cell lines and tissues and investigated their role as potential tumor suppressors in vitro and in vivo. Transfection of osteosarcoma cells (n = 6) with miR-127-3p and miR-376a-3p mimics significantly inhibited proliferation and reduced the colony formation capacity of these cells. In contrast, we could not detect any influence of miRNA restoration on cell cycle and apoptosis induction. The effects of candidate miRNA restoration on tumor engraftment and growth in vivo were analyzed using a chicken chorioallantoic membrane (CAM) assay. Cells transfected with mir-127-3p and miR-376a-3p showed reduced tumor take rates and tumor volumes and a significant decrease of the cumulative tumor volumes to 41% and 54% compared to wildtype cells. The observed tumor suppressor function of both analyzed miRNAs indicates these miRNAs as potentially valuable targets for the development of new therapeutic strategies for the treatment of osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Fellenberg

Lehner

Saehr

et al. 2019

Cancers

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“…AREG is essential for estrogen receptor-targeted therapeutic response ( 31 ). NRP1 has been previously shown to promote tumorigenesis by enhancing angiogenesis ( 32 ) and NRP1-positive cells have been reported to have tumor-initiating properties ( 33 ). Thus the upregulation of these genes may result from indirect effects independent of cAMP, a possibility we will investigate.…”

Section: Discussionmentioning

confidence: 99%

Parathyroid Hormone-Related Protein Negatively Regulates Tumor Cell Dormancy Genes in a PTHR1/Cyclic AMP-Independent Manner

Johnson

Sun

et al. 2018

Front. Endocrinol.

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Parathyroid hormone-related protein (PTHrP) expression in breast cancer is enriched in bone metastases compared to primary tumors. Human MCF7 breast cancer cells “home” to the bones of immune deficient mice following intracardiac inoculation, but do not grow well and stain negatively for Ki67, thus serving as a model of breast cancer dormancy in vivo. We have previously shown that PTHrP overexpression in MCF7 cells overcomes this dormant phenotype, causing them to grow as osteolytic deposits, and that PTHrP-overexpressing MCF7 cells showed significantly lower expression of genes associated with dormancy compared to vector controls. Since early work showed a lack of cyclic AMP (cAMP) response to parathyroid hormone (PTH) in MCF7 cells, and cAMP is activated by PTH/PTHrP receptor (PTHR1) signaling, we hypothesized that the effects of PTHrP on dormancy in MCF7 cells occur through non-canonical (i.e., PTHR1/cAMP-independent) signaling. The data presented here demonstrate the lack of cAMP response in MCF7 cells to full length PTHrP(1–141) and PTH(1–34) in a wide range of doses, while maintaining a response to three known activators of adenylyl cyclase: calcitonin, prostaglandin E2 (PGE2), and forskolin. PTHR1 mRNA was detectable in MCF7 cells and was found in eight other human breast and murine mammary carcinoma cell lines. Although PTHrP overexpression in MCF7 cells changed expression levels of many genes, RNAseq analysis revealed that PTHR1 was unaltered, and only 2/32 previous PTHR1/cAMP responsive genes were significantly upregulated. Instead, PTHrP overexpression in MCF7 cells resulted in significant enrichment of the calcium signaling pathway. We conclude that PTHR1 in MCF7 breast cancer cells is not functionally linked to activation of the cAMP pathway. Gene expression responses to PTHrP overexpression must, therefore, result from autocrine or intracrine actions of PTHrP independent of PTHR1, through signals emanating from other domains within the PTHrP molecule.

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“…Neuropilin1 (NRP1) is a cell surface glycoprotein involved in various cellular processes, including angiogenesis, cell migration, and axon growth [6]. Especially in various types of tumor, NRP1 has a critical role in cell migration, invasion and angiogenesis, promoting tumor progression [7].…”

Section: Introductionmentioning

confidence: 99%

Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages

Kang

Gil

Kim

2020

JCM

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Neuropilin1 (NRP1) plays a critical role in tumor progression and immune responses. Although the roles of NRP1 in various tumors have been investigated, the clinical relevance of NRP1 expression in stomach adenocarcinoma (STAD) has not been studied. To investigate the use of NRP1 as a prognostic biomarker of STAD, we analyzed NRP1 mRNA expression and its correlation with patient survival and immune cell infiltration using various databases. NRP1 mRNA expression was significantly higher in STAD than normal tissues, and Kaplan-Meier survival analysis showed that NRP1 expression was significantly associated with poor prognosis in patients with STAD. To elucidate the related mechanism, we analyzed the correlation between NRP1 expression and immune cell infiltration level. In particular, the infiltration of immune-suppressive cells, such as regulatory T (Treg) cells and M2 macrophage, was significantly increased by NRP1 expression. In addition, the expression of interleukin (IL)-35, IL-10, and TGF-β1 was also positively correlated with NRP1 expression, resulting in the immune suppression. Collectively in this study, our integrated analysis using various clinical databases shows that the significant correlation between NRP1 expression and the infiltration of Treg cells and M2 macrophage explains poor prognosis mechanism in STAD, suggesting the clinical relevance of NRP1 expression as a prognostic biomarker for STAD patients.

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NRP1-positive lung cancer cells possess tumor-initiating properties

Cited by 29 publications

References 37 publications

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Tumor Suppressor Function of miR-127-3p and miR-376a-3p in Osteosarcoma Cells

Parathyroid Hormone-Related Protein Negatively Regulates Tumor Cell Dormancy Genes in a PTHR1/Cyclic AMP-Independent Manner

Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages

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