Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinoma<i>via</i>creating a cancer-supportive niche

Xu, Xiaowen; Chang, Wenjun; Yuan, Jie; Han, Xue; Tan, Xiaojie; Ding, Yibo; Luo, Yanxin; Cai, Hui; Liu, Yan; Gao, Xianhua; Liu, Qizhi; Ye, Yu; Du, Yan; Wang, Hao; Ma, Long; Wang, Jianping; Chen, Kun; Ding, Yan‐Qing; Fu, Chuangang; Cao, Guangwen

doi:10.18632/oncotarget.5985

Cited by 46 publications

(59 citation statements)

References 39 publications

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“…These may include FGF2, whose expression was upregulated, in agreement with previous findings (Casanovas et al, 2005). Also, POSTN may promote stromal cell survival and expansion (Xu et al, 2016) in an autocrine fashion (B) Relative F4/80 + area (mean percentage values ± SEM) in PNETs of 15-to 17-week-old WT or Postn À/À mice. WT mice, IgG control (4 weeks PTI): n = 30 tumors from 4 mice; anti-VEGFA (4 weeks PTI): n = 37 from 4 mice; anti-VEGFA (6 weeks PTI): n = 34 from 3 mice.…”

Section: Discussionsupporting

confidence: 87%

Periostin Limits Tumor Response to VEGFA Inhibition

et al. 2018

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Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy. POSTN deficiency also impeded the upregulation of basic fibroblast growth factor (FGF2), an adaptive mechanism previously implicated in PNET evasion from antiangiogenic therapy. Higher POSTN expression correlated with markers of M2-like macrophages in human PNETs, and depleting macrophages with a colony-stimulating factor 1 receptor (CSF1R) antibody inhibited PNET revascularization and progression under VEGFA blockade despite continued POSTN production. These findings suggest a role for POSTN in orchestrating resistance to anti-VEGFA therapy in PNETs.

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Section: Discussionsupporting

confidence: 87%

Periostin Limits Tumor Response to VEGFA Inhibition

et al. 2018

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“…Fifteen of the 21 DEGs in BMets are ECM-related genes (Table S8). Whereas 13 of the 21 genes are reportedly expressed exclusively in the stroma [5,[21][22][23][24][25][26][27][28][29][30][31][32], we have determined that LRRC15 is expressed in both the stroma and the epithelial compartment ( Fig. 3).…”

Section: Discussionmentioning

confidence: 83%

Genes associated with bowel metastases in ovarian cancer

Mariani

Wang

Oberg

et al. 2019

Gynecologic Oncology

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We identified 21 genes overexpressed in ovarian cancer (OC) bowel metastases compared to primary tumors. • High expression of these genes in primary OCs is associated with a need of complex bowel surgery and poor prognosis.• These genes may help identify potential therapeutic targets of malignant bowel obstruction in OC. a b s t r a c tObjective. This study is designed to identify genes and pathways that could promote metastasis to the bowel in high-grade serous ovarian cancer (OC) and evaluate their associations with clinical outcomes.Methods. We performed RNA sequencing of OC primary tumors (PTs) and their corresponding bowel metastases (n = 21 discovery set; n = 18 replication set). Differentially expressed genes (DEGs) were those expressed at least 2-fold higher in bowel metastases (BMets) than PTs in at least 30% of patients (P b .05) with no increased expression in paired benign bowel tissue and were validated with quantitative reverse transcription PCR. Using an independent OC cohort (n = 333), associations between DEGs in PTs and surgical and clinical outcomes were performed. Immunohistochemistry and mouse xenograft studies were performed to confirm the role of LRRC15 in promoting metastasis.Results. Among 27 DEGs in the discovery set, 21 were confirmed in the replication set: SFRP2, Col11A1, LRRC15, ADAM12, ADAMTS12, MFAP5, LUM, PLPP4, FAP, POSTN, GRP, MMP11, MMP13, C1QTNF3, EPYC, DIO2, KCNA1, NETO1, NTM, MYH13, and PVALB. Higher expression of more than half of the genes in the PT was associated with an increased requirement for bowel resection at primary surgery and an inability to achieve complete cytoreduction. Increased expression of LRRC15 in BMets was confirmed by immunohistochemistry and knockdown of LRRC15 significantly inhibited tumor progression in mice.Conclusions. We identified 21 genes that are overexpressed in bowel metastases among patients with OC. Our findings will help select potential molecular targets for the prevention and treatment of malignant bowel obstruction in OC. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

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“…POSTN is an extracellular matrix N-glycoprotein with known functions in bone development, maturation and repair, tissue repair, and epithelial–mesenchymal transition (EMT) [ 13 , 14 , 15 ]. POSTN has been shown to regulate cancer cell proliferation, angiogenesis, invasion, and metastasis by interacting with integrins such as αVβ1, αVβ3, αVβ5, and α6β4, which activate the Akt/PKB and FAK-mediated signalling pathways [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

Ratajczak‐Wielgomas

Kmiecik

Grzegrzółka

et al. 2020

IJMS

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Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

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Periostin expression in intra-tumoral stromal cells is prognostic and predictive for colorectal carcinomaviacreating a cancer-supportive niche

Cited by 46 publications

References 39 publications

Periostin Limits Tumor Response to VEGFA Inhibition

Periostin Limits Tumor Response to VEGFA Inhibition

Genes associated with bowel metastases in ovarian cancer

Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

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