Analysis of differential gene expression in colorectal cancer and stroma using fluorescence-activated cell sorting purification

Smith, Myles; Culhane, Aedín C.; Donovan, Maryanne; Coffey, J. Calvin; Barry, B. D.; Kelly, M. A.; Higgins, Desmond G.; Wang, Jeffrey Tze-Yee; Kirwan, W. O.; Cotter, Thomas G.; Redmond, H. P.

doi:10.1038/sj.bjc.6604931

Cited by 36 publications

(20 citation statements)

References 52 publications

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“…This fact can be due to a higher level of stromal components in the peripheral part of the tumor than in its central part. The change of the expression profile corresponds to data obtained from colorectal cancer research that reported the predominance of proteins forming components of extracellular matrix: collagens, tissue inhibitors of matrix metalloproteins (COL6A3, COL1A2, POSTN, TIMP2 and others) at the peripheral part of the tumor [10].…”

Section: Discussionsupporting

confidence: 77%

Transcriptomic Analysis of Melanoma Cells Extracted From Different Sites of the Primary Tumor

Aksenenko¹,

Komina²,

Palkina³

et al. 2018

Sib. onkol. ž.

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. For citation: Aksenenko M.B., Komina A.V., Palkina N.V., Averchuk A.S., Rybnikov Yu.A., Dyhno Yu.A., Ruksha T.G. transcriptomic analysis of melanoma cells extracted from different sites of the primary tumor. Siberian Journal of Oncology. 2018; 17 (4): 59-66. -doi: 10.21294/1814-4861-2018 Введение. Внутриопухолевая гетерогенность представляет собой характерную черту большинства злокачественных новообразований, в том числе и меланомы кожи. данное свойство является одним из препятствий для проведения эффективной таргетной терапии, поскольку у различных субклонов опухолевых клеток наблюдается вариабельная чувствительность к данным препаратам. С современ-ных позиций терапия злокачественных новообразований требует персонифицированного подхода для каждого конкретного пациента. цель исследования -оценка возможных различий между тканями меланомы, выделенными из различных участков первичной опухоли одного пациента на транскрип-томном уровне. материал и методы. В работе были использованы культуры клеток меланомы, полу-ченные из центральной и периферической частей первичной опухоли двух пациентов. Исследование транскриптомов клеток проводили методом микрочипирования с последующим биоинформатическим анализом. результаты. В клетках меланомы первого пациента, полученных из центрального и пери-ферического участков одной опухоли, не было выявлено различий по транскриптомному профилю. У второго пациента имели место существенные различия (по 2953 транскриптам из 48226). В клетках, полученных из центрального участка опухоли, выявлено повышение мРНК генов, кодирующих белки, ассоциированные с иммунным ответом опухоли, транспортные белки ABC-семейства, сигнальные молекулы класса цитокинов. В культуре клеток, выделенной из периферического участка этой же опу-холи, зарегистрировано увеличение уровня мРНК генов, кодирующих белки внеклеточного матрикса и воспалительного ответа. В целом различия между субклонами клеток второго пациента касались ряда сигнальных каскадов, играющих ведущую роль в онкогенезе (MApK, pI3K-Akt-mToR, VEGFA-VEGFR2 и др). заключение. Проведенное исследование позволяет оценить возможные различия между клетками внутри опухоли на транскрипционном уровне с целью поиска новых подходов для персонифицированной терапии.Ключевые слова: меланома, гетерогенность, транскриптом, микроокружение. TRANSCRIPTOMIC ANALYSIS OF MELANOMA CELLS EXTRACTED FROM DIFFERENT SITES OF THE PRIMARY TuMOR AbstractIntroduction. Intratumor heterogeneity is a characteristic feature for most malignant tumors, including cutaneous melanoma. This property represents one of the main obstacles for effective targeted therapy, due to the different sensitivity to chemotherapeutic agents on various tumor cells subclones. Treatment of malignant tumors requires an individual approach to choose the most appropriate treatment regimen. The purpose of the study was to evaluate differences in melanoma tissue samples obtained from different parts of one patient's primary tumor at the transcriptomic level. Material and Methods. Melanoma cell cultures obtained from...

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Section: Discussionsupporting

confidence: 77%

Transcriptomic Analysis of Melanoma Cells Extracted From Different Sites of the Primary Tumor

Aksenenko¹,

Komina²,

Palkina³

et al. 2018

Sib. onkol. ž.

View full text Add to dashboard Cite

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“…COL6 upregulation has been reported in various aspects of tumor progression. Malignant cancer cells can also express COL6; this has been reported for the mammary gland (18), the colon (35,36), pancreatic ductal adenocarcinomas (37), and hepatocarcinomas (38). Thus, the source of ETP in the tumor microenvironment may be heterogeneous, with signals cooperatively influencing cancer cell behavior through paracrine and autocrine pathways.…”

Section: Discussionmentioning

confidence: 89%

Adipocyte-derived endotrophin promotes malignant tumor progression

Park

Scherer²

2012

J. Clin. Invest.

290

335

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Adipocytes represent a major cell type in the mammary tumor microenvironment and are important for tumor growth. Collagen VI (COL6) is highly expressed in adipose tissue, upregulated in the obese state, and enriched in breast cancer lesions and is a stimulator of mammary tumor growth. Here, we have described a cleavage product of the COL6α3 chain, endotrophin (ETP), which serves as the major mediator of the COL6-mediated tumor effects. ETP augmented fibrosis, angiogenesis, and inflammation through recruitment of macrophages and endothelial cells. Moreover, ETP expression was associated with aggressive mammary tumor growth and high metastatic growth. These effects were partially mediated through enhanced TGF-β signaling, which contributes to tissue fibrosis and epithelial-mesenchymal transition (EMT) of tumor cells. Our results highlight the crucial role of ETP as an obesity-associated factor that promotes tumor growth in the context of adipocyte interactions with tumor and stromal cells.

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“…Moreover, a spectrum of studies has reported the suppression of MYC by miRNAs, including let-7a (40), miR-23a/b (41) and miR-145 (42), in various cancer types. Furthermore, the overexpression of stromal genes, such as collagen type I α2 chain (COL1A2), was also detected in CRC (43). …”

Section: Discussionmentioning

confidence: 99%

Identification of potential therapeutic targets for colorectal cancer by bioinformatics analysis

et al. 2016

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The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package. Next, functional and pathway enrichment analysis of the DEGs was performed using the Database for Annotation Visualization and Integrated Discovery. The protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes database. Utilizing WebGestalt, the potential microRNAs (miRNAs/miRs) of the DEGs were screened and the integrated miRNA-target network was built. A cohort of 1,347 DEGs was identified, the majority of which were mainly enriched in cell cycle-related biological processes and pathways. Cyclin-dependent kinase 1 (CDK1), cyclin B1 (CCNB1), MAD2 mitotic arrest deficient-like 1 (MAD2L1) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were prominent in the PPI network, while the over-represented genes in the integrated miRNA-target network were SRY (sex determining region Y)-box 4 (SOX4; targeted by hsa-mir-129), v-myc avian myelocytomatosis viral oncogene homolog (MYC; targeted by hsa-let-7c and hsa-mir-145) and cyclin D1 (CCND1; targeted by hsa-let-7b). CDK1, CCNB1 and CCND1 were also associated with the p53 signaling pathway. Overall, several genes associated with the cell cycle and p53 pathway were identified as biomarkers for CRC. CDK1, CCNB1, MAD2L1, BUB1B, SOX4, collagen type I α2 chain and MYC may play significant roles in CRC progression by affecting the cell cycle-related pathways, while CDK1, CCNB1 and CCND1 may serve as crucial regulators in the p53 signaling pathway. Furthermore, SOX4, MYC and CCND1 may be targets of miR-129, hsa-mir-145 and hsa-let-7c, respectively. However, further validation of these data is required.

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Analysis of differential gene expression in colorectal cancer and stroma using fluorescence-activated cell sorting purification

Cited by 36 publications

References 52 publications

Transcriptomic Analysis of Melanoma Cells Extracted From Different Sites of the Primary Tumor

Transcriptomic Analysis of Melanoma Cells Extracted From Different Sites of the Primary Tumor

Adipocyte-derived endotrophin promotes malignant tumor progression

Identification of potential therapeutic targets for colorectal cancer by bioinformatics analysis

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