The laminin-derived peptide C16 regulates GPNMB expression and function in breast cancer

Smuczek, Basilio; Santos, Emerson de Souza; Siqueira, Adriane Sousa de; Pinheiro, João de Jesus Viana; Freitas, Vanessa M.; Jaeger, Ruy Gastaldoni

doi:10.1016/j.yexcr.2017.07.005

Cited by 16 publications

(14 citation statements)

References 59 publications

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“…Western blotting demonstrated that GPNMB was indeed expressed highly in SUM-159 and MDA-MB-231 cells and lowly in MCF7 and MCF10A cells corroborating prior studies (Fig. S7A)[31]. Next, to study the role of GPNMB in the context of tumor microenvironment, we assessed the expression of GPNMB in SUM-159 cells in mono- or co-culture with CAFs (CAF3).…”

Section: Resultssupporting

confidence: 82%

“…We did indeed observe similar association between GPNMB and integrins and MMPs in our RNA-seq data (Table S9). GPNMB interaction with integrin was also shown to activate SRC and FAK signaling, which regulate cell migration[31, 42]. Our results taken together with the current findings suggested that GPNMB plays a crucial role in cancer invasion in 3D microenvironment.…”

Section: Discussionsupporting

confidence: 76%

“…Smuczek et al . showed that C16, a laminin-111 subunit, could enhance GPNMB expression and promote MDA-MB-231 cell migration[31]. It was suggested that C16 was produced through cell-induced proteolysis of the ECM through MMP9 and MMP9 has been shown to be secreted by CAFs[44, 45].…”

Section: Discussionmentioning

confidence: 99%

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A Human Organotypic Microfluidic Tumor Model Permits Investigation of the Interplay between Patient-Derived Fibroblasts and Breast Cancer Cells

et al. 2019

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Tumor-stroma interactions significantly influence cancer cell metastasis and disease progression. These interactions partly comprise crosstalk between tumor and stromal fibroblasts, but the key molecular mechanisms within the crosstalk that govern cancer invasion are still unclear. Here we adapted our previously developed microfluidic device as a 3D in vitro organotypic model to mechanistically study tumor-stroma interactions by mimicking the spatial organization of the tumor microenvironment on a chip. We co-cultured breast cancer and patient-derived fibroblast cells in 3D tumor and stroma regions, respectively, and combined functional assessments, including cancer cell migration, with transcriptome profiling to unveil the molecular influence of tumor-stroma crosstalk on invasion. This led to the observation that cancer-associated fibroblasts (CAF) enhanced invasion in 3D by inducing expression of a novel gene of interest, GPNMB, in breast cancer cells, resulting in increased migration speed. Importantly, knockdown of GPNMB blunted the influence of CAF on enhanced cancer invasion. Overall, these results demonstrate the ability of our model to recapitulate patient-specific tumor microenvironments to investigate the cellular and molecular consequences of tumor-stroma interactions.

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Section: Resultssupporting

confidence: 82%

Section: Discussionsupporting

confidence: 76%

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A Human Organotypic Microfluidic Tumor Model Permits Investigation of the Interplay between Patient-Derived Fibroblasts and Breast Cancer Cells

et al. 2019

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“…As one of the major components of ECM, laminins were correlated with a variety of tumor initiation and progression. For example, laminins regulated ovarian cancer cell proliferation [45], thyroid carcinoma cell growth and differentiation [46], cell differentiation in colon cancer cells [47, 48], and invasion of highly aggressive MDA-MB-231 breast cancer cells [49]. In this study, a series of laminins including LAMA1, LAMA2, LAMA3, LAMA4, LAMA5 LAMB1, LAMB2, LAMC1, and LAMC2 were upregulated in invasive NFPAs.…”

Section: Discussionmentioning

confidence: 76%

TMT-based quantitative proteomics revealed follicle-stimulating hormone (FSH)-related molecular characterizations for potentially prognostic assessment and personalized treatment of FSH-positive non-functional pituitary adenomas

Wang

Cheng

et al. 2019

EPMA Journal

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BackgroundNon-functional pituitary adenoma (NFPA) is highly heterogeneous with different hormone expression subtypes. Of them, follicle-stimulating hormone (FSH)-positive expression is an important subtype of NFPAs. It is well-known that FSH exerted its functions through binding its receptor. However, the expression rate of FSH receptor was significantly higher in aggressive pituitary adenomas. This study aimed to investigate the molecular characteristics of FSH-positive NFPAs for effective stratification of patient, target treatment, prognostic assessment, and personalized treatment of FSH-positive NFPAs.MethodsTandem mass tag (TMT)-based quantitative proteomics was used to investigate differentially expressed proteins (DEPs) between FSH-positive and negative NFPAs. Gene ontology and KEGG pathway enrichment analyses were used to analyze the DEPs. Differentially expressed genes (DEGs) between invasive and non-invasive NFPAs from GEO database were analyzed with pathway enrichment analysis. Protein-protein interaction (PPI) networks were constructed based on DEPs in excetral cellular matrix (ECM)-receptor interaction, focal adhesion, and PI3K-Akt pathways. Cytoscape was used to obtain most significant modules. Western blot was used to validate the expressions of upregulated proteins (ITGA1, ITGA6, and ITGB4), the expression and phosphorylated status of Akt in PI3K-Akt pathway, and the expression of FSH receptors in FSH-positive relative to negative NFPAs.ResultsA total of 594 DEPs (374 upregulated and 220 downregulated) were identified between FSH-positive and negative NFPAs. Nineteen KEGG pathway networks were identified to involve DEPs, and reveal molecular differences between FSH-positive and negative NFPAs, including three important pathways that were significantly associated with tumor invasiveness and aggressiveness: ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways. Further, focal adhesion pathway was also confirmed with invasiveness-related NFPA DEG data that were derived from GEO database. Moreover, the significantly upregulated DEPs (ITGA1, ITGA6, and ITGB4) that were associated with tumor invasiveness and aggressiveness were confirmed by immunoaffinity analysis in FSH-positive vs. negative NFPAs. Also, the phosphorylation level but not its expression level of AKT in PI3K-AKT signaling was significantly increased, and the expression level of FSH receptor was significantly increased in FSH-positive relative to negative NFPAs. Also, overlapping analysis of 594 DEPs and 898 DEGs revealed 45 invasiveness-related DEPs, including 11 upregulated DEPs (ITGA6, FARP1, PALLD, PPBP, LIMA1, SCD, UACA, BAG3, CLU, PLEC, and GATM) that were also upregulated genes in invasive NFPAs, and 8 downregulated DEPs (ALCAM, HP, FSTL4, IL13RA2, NPTX2, DPP6, CRABP2, and SLC27A2) that were also downregulated genes in invasive NFPAs.ConclusionsFSH-positive expression was an important NFPA subtype. It was the first time for this study to reveal FSH-related proteomic variations and the corresponding molecular netw...

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“…domínios específicos nos terminais amino e carboxil da cadeia a, promovendo adesão celular, e modulando diversos processos celulares e morfogênicos(SULEIMAN;ZHANG;ROTH;HEUSER et al, 2013;YAO, 2017).Peptídeos produzidos a partir da proteólise da laminina têm efeitos biológicos importantes em condições fisiológicas ou em doenças como câncer(FREITAS; JAEGER, 2002; FREITAS; VILAS-BOAS; PIMENTA; LOUREIRO et al, 2007;SMUCZEK;SANTOS;SIQUEIRA;PINHEIRO et al, 2017). Atualmente, já foram descritas 5 cadeias a, 4 cadeias b e 3 cadeias g, arranjadas em 20 combinações em mamíferos.…”

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Estudo da matriz extracelular metanéfrica e dos efeitos do diabetes >i<mellitus>/i< materno sobre o desenvolvimento renal em camundongos.

Morais¹

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The laminin-derived peptide C16 regulates GPNMB expression and function in breast cancer

Cited by 16 publications

References 59 publications

A Human Organotypic Microfluidic Tumor Model Permits Investigation of the Interplay between Patient-Derived Fibroblasts and Breast Cancer Cells

A Human Organotypic Microfluidic Tumor Model Permits Investigation of the Interplay between Patient-Derived Fibroblasts and Breast Cancer Cells

TMT-based quantitative proteomics revealed follicle-stimulating hormone (FSH)-related molecular characterizations for potentially prognostic assessment and personalized treatment of FSH-positive non-functional pituitary adenomas

Estudo da matriz extracelular metanéfrica e dos efeitos do diabetes >i<mellitus>/i< materno sobre o desenvolvimento renal em camundongos.

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