Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

Yoshimura, Tsuyoshi; Nagahara, Makoto; Kuo, Calvin; Turner, Roderick R.; Soon‐Shiong, Patrick; Hoon, Dave S.B.

doi:10.4161/epi.6.8.16063

Cited by 23 publications

(26 citation statements)

References 47 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding is in accordance with a possible anti-angiogenic effect and inhibition of tumor dissemination by SPARC, in accord with results published recently [20,47]. …”

Section: Discussionsupporting

confidence: 93%

Relationship between the Expression of the Extracellular Matrix Genes SPARC, SPP1, FN1, ITGA5 and ITGAV and Clinicopathological Parameters of Tumor Progression and Colorectal Cancer Dissemination

Viana¹,

Affonso²,

Silva³

et al. 2012

Oncology

View full text Add to dashboard Cite

Objective: To evaluate the relationship between the expression of the extracellular matrix (ECM) genes SPARC, SPP1, FN1, ITGA5 and ITGAV and the histopathologic parameters of neoplastic progression and colorectal carcinoma (CRC) dissemination. Methods: A retrospective study was conducted in 114 patients with stage I–IV CRC who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry (IHC) assays were performed in samples obtained from the primary tumors. The correlation between the expression of these markers and the expression of p53, Bcl-2, Ki67, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor was assessed with the Spearman coefficient (r). Results: The ITGAV gene was found to be significantly amplified in tumors with positive perineural invasion (p = 0.028). Expression of the SPARC, SPP1, FN1, ITGA5 and ITGAV genes did not correlate with TNM staging. A direct relationship between ITGAV and EGFR expression (r = 0.774; p < 0.001) was observed by IHC. Conclusions: ECM gene expression did not correlate with classical prognostic factors for CRC, but overexpression of the ITGAV gene and protein was correlated with an increased risk of perineural invasion. The relationship between ITGAV and EGFR expression suggests the possibility of crosstalk in this signal pathway.

show abstract

“…This finding is in accordance with a possible anti-angiogenic effect and inhibition of tumor dissemination by SPARC, in accord with results published recently [20,47]. …”

Section: Discussionsupporting

confidence: 93%

Relationship between the Expression of the Extracellular Matrix Genes SPARC, SPP1, FN1, ITGA5 and ITGAV and Clinicopathological Parameters of Tumor Progression and Colorectal Cancer Dissemination

Viana¹,

Affonso²,

Silva³

et al. 2012

Oncology

View full text Add to dashboard Cite

show abstract

“…63), it was not surprising to find increased SPARC levels in early stages of differentiation of growth-arrested nonproliferating fibroblasts and macrophages in response to inflammatory stimuli (Supplemental Figures 5 and 6) and hence, the lack of cancerous compartment. Our findings regarding SPARC protein expression in the human bladder tumor and carcinogenesis model in the Sparc +/+ mice may explain the apparently paradoxical reports in which expression of SPARC protein in cancer is decreased due to promoter methylation, while being overexpressed in the tumor associated stroma (26,(50)(51)(52)(53)(54)(55)(56). In our study, we show that SPARC protein expression increased in fibroblasts and macrophages in vitro in response to stimulation by cancer cells, the prototype ROS, and H 2 O 2 as well as 8-isoprostane, another marker of oxidative tissue damage that further contributes to inflammation and ROS production.…”

Section: Discussionmentioning

confidence: 59%

Loss of SPARC in bladder cancer enhances carcinogenesis and progression

Said¹,

Frierson²,

Sänchez‐Carbayo³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

Secreted protein acidic and rich in cysteine (SPARC) has been implicated in multiple aspects of human cancer. However, its role in bladder carcinogenesis and metastasis are unclear,with some studies suggesting it may be a promoter and others arguing the opposite. Using a chemical carcinogenesis model in Sparc-deficient mice and their wild-type littermates, we found that loss of SPARC accelerated the development of urothelial preneoplasia (atypia and dysplasia), neoplasia, and metastasis and was associated with decreased survival. SPARC reduced carcinogen-induced inflammation and accumulation of reactive oxygen species as well as urothelial cell proliferation. Loss of SPARC was associated with an inflammatory phenotype of tumor-associated macrophages and fibroblasts, with concomitant increased activation of urothelial and stromal NF-κB and AP1 in vivo and in vitro. Syngeneic spontaneous and experimental metastasis models revealed that tumorand stroma-derived SPARC reduced tumor growth and metastasis through inhibition of cancer-associated inflammation and lung colonization. In human bladder tumor tissues, the frequency and intensity of SPARC expression were inversely correlated with disease-specific survival. These results indicate that SPARC is produced by benign and malignant compartments of bladder carcinomas where it functions to suppress bladder carcinogenesis, progression, and metastasis.

show abstract

“…Quantitative DNA methylation analysis was performed using Matrix-Assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry (MALDI-TOF-MS) as previously described. 28,29 Five primer sets were designed with EpiDesigner (SEQUENOM) to assess methylation status of the promoter region from -2055 bp to +117 bp (intron 1) of REG1A (Fig. S5).…”

Section: Methodsmentioning

confidence: 99%

“…No significant differences were observed between DNA methylation level of We previously reported that DNA methylation status of promoter region of tumor-related genes is closely related to gene expression and prognosis of melanoma patients. [25][26][27] This approach was successfully used previously by our groups with MassARRAY analysis in colon 28 and breast cancer tumors. 29 Among the melanoma patients in this study, all adjuvant group patients were pathologically diagnosed as AJCC stage IIIb or IIIc with multiple LN metastasis and treated with adjuvant chemotherapy after surgery.…”

Section: Reg1amentioning

confidence: 99%