Overexpression of S100A4 is closely associated with progression of colorectal cancer

Cho, Yong-Gu; Kim, Changjae; Nam, Suk-Woo; Yoon, Sung Hyun; Lee, Sug-Hyung; Yoo, Nam-Jin; Lee, Jung-Young; Park, Won-Sang

doi:10.3748/wjg.v11.i31.4852

Cited by 48 publications

(37 citation statements)

References 17 publications

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“…17 , 18 High S100A4 levels in colorectal tumors are associated with aggressive growth, metastasis, poor prognosis, and shortened patient survival times. 33 However, its role in colon cancer progression remains to be adequately tested. Using an AOM/DSS-induced CRC model, we also detected a high level of S100A4 expression in the colon during the process of CRC (Fig.…”

Section: Resultsmentioning

confidence: 99%

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S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

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S100A4 plays important roles in tumor development and metastasis, but its role in regulating inflammation and colitis-associated tumorigenesis has not been well characterized. Here, we report that S100A4 expression was increased in azoxymethane (AOM) and dextran sulfate sodium (DSS) induced colorectal cancer (CRC) in mice. After AOM/DSS treatment, both S100A4-TK mice with the selective depletion of S100A4-expressing cells and S100A4-deficient (S100A4−/−) mice developed fewer and smaller tumors than wild-type (WT) control littermates. Furthermore, S100A4−/− mice were resistant to DSS-induced colitis, reduced infiltration of macrophages, and the diminished production of proinflammatory cytokines. Further studies revealed that reduced colon inflammation and colorectal tumor development in S100A4−/− mice were partly due to the dampening of nuclear factor (NF)-κB activation in macrophages. Furthermore, the administration of a neutralizing S100A4 antibody to WT mice significantly decreased AOM/DSS-induced colon inflammation and tumorigenesis. These results indicate that S100A4 amplifies an inflammatory microenvironment that promotes colon tumorigenesis and provides a promising therapeutic strategy for treatment of inflammatory bowel disease and prevention of colitis-associated colorectal carcinogenesis.

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Section: Resultsmentioning

confidence: 99%

“…33 High S100A4 levels in colorectal tumors are associated with metastasis, poor prognosis, and shortened patient survival times. 34 Recently, we found S100A4 promotes colitis development by enhancing host adhesion and colonization of Citrobacter rodentium through the S100A4-mediated host inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Zhang

Hou

et al. 2018

OncoImmunology

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“…However, there are also some contradictory reports in this series. According to some studies, there is no significant correlation between the expression of S100A4 and OS in colon cancer, non-small cell lung carcinoma (NSCLC) and melanoma (25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of cytoplasmic expression of S100A4 protein in endometrial carcinoma

et al. 2014

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Abstract. The S100A4 protein, a member of the S100 family of calcium-binding proteins, has been considered as a candidate prognostic marker in patients with cancer. The present study was conducted to evaluate the prognostic value of S100A4 and to examine its correlation with the clinicopathological parameters and the overall survival and progression-free survival in patients with endometrial carcinoma (EC). To do this, we performed immunohistochemistry of formalin-fixed tissue sections obtained from 135 cases of EC. In addition, we quantified the level of S100A4 mRNA using the quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). The cytoplasmic expression of S100A4 protein was observed in 35 cases (25.9%). There was a significant association between the expression of S100A4 and clinicopathological parameters such as histologic grade, FIGO stage, lymph node metastasis and loss of progesterone receptor (PR). qRT-PCR demonstrated that the level of S100A4 mRNA was significantly higher in ECs as compared with normal endometrium. The cytoplasmic expression of S100A4 had a significant correlation with shorter overall survival and progression-free survival on the Kaplan-Meyer survival analysis. In multivariate analysis, there was a significant correlation between S100A4 expression and a poorer OS. In conclusion, our results indicate that S100A4 may be a biological marker indicating the recurrence and poor prognosis in patients with EC.

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“…As for our study, we tried to show the relationship of the number and percentage of metastatic lymph nodes with S100A4 rather than the number of ideal lymph nodes that should be excised. The prognostic role of S100A4 existence has still been discussed in terms of colorectal cancer (37,(42)(43)(44)(45)(46)(47). These disaccords may result from subtle diversities such as the number of patients, observation period, stage distribution, tissue fixation methods, antibody use and cut-off for positivity.…”

Section: Discussionmentioning

confidence: 99%

Kolon Kanserinde S100A4 Ekspresyonunun Klinik ve Patolojik Önemi

2016

Mustafa Kemal Üniversitesi Tıp Dergisi

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Aim: Because the S100A4 gene is recognized as a marker in metastasis (in vitro, in vivo) and invasion, this study aimed to determine the clinical and pathological significance of S100A4 expression in patients with colorectal cancer.Material and Methods: S100A4 expression was evaluated through samples taken from blocked resection material from 111 colon cancer patients and through immunohistochemical staining scores (IHCSS). We studied the relationships between IHCSS and patient age, gender, tumor localization, tumor diameter, surgical procedure, perineural invasion, perivascular invasion, T stage, N stage, M stage, disease stage, tumor grade, and metastatic lymph node ratio, comparing survival and mortality rates. Results:No statistically significant difference was spotted when comparing IHCSS against patient gender, patient age, tumor localization, surgery performed, or tumor diameter. As for perivascular invasion, lymph node involvement, and degree of metastasis, all of which are considered to intensify tumor progression and aggressivity, each increased in direct proportion to IHCSS. As a result, because S100A4 expression influences tumor metastasis and invasion, an increase in S100A4 proteins may herald a poor prognosis. Conclusion:Thus, S100A4 expression may be useful for determining more effective treatment strategies in colorectal cancer. Further studies are needed at the clinical level to confirm the practicality of using S100A4 expression to augment patient treatment.Key words: Colon cancer, S100A4, calcium binding proteins ÖZET Amaç: Bu çalışma, invitro ve invivo metastaz ve invazyon belirteci olarak gösterilmiş olan S100A4 ekspresyonunun kolorektal kanserli hastalarda klinik ve patolojik önemini belirlemek amacıyla yapılmıştır. Gereç ve Yöntem:111 kolon kanserli hastanın bloklanmış rezeksiyon materyallerinden kesitler alınmış ve immunhistokimya boyama skorlaması (İHKBS) yapılarak S100A4 ekspresyonu değerlendirilmiştir. İHKBS ile hasta yaşı, cinsiyeti, tümör lokalizasyonu, tümör çapı, ameliyat tipi, perinöral invazyon varlığı, perivasküler invazyon varlığı, T evresi, N evresi, M evresi, hastalık evresi, tümör grade'i, metastatik lenf nodu yüzdesi, sağkalım ve mortalite arasındaki ilişki karşılaştırılmıştır. Bulgular:Hasta cinsiyeti, hasta yaşı, tümör lokalizyonu, ameliyat tipi ve tümör çapı ile İHKBS arasında yapılan karşılaştırmalarda anlamlı bir istatiksel fark elde edilmedi. Tümör progresyonu ve agresivitesini arttıran perivasküler invazyon, perinöral invazyon, lenf nodu tutulumu ve metastaz parametrelerinin ise İHBS ile doğru orantılı olarak arttığı gözlenmiştir.Sonuç: Sonuç olarak tümör metastazı ve invazyonunu artıran S100A4'nün ekspresyonundaki artışın kötü prognoz göstergesi olabileceği değerlendirilmiştir. Kötü prognostik faktörlerle ilişkili olan S100A4 ekspresyonunun kolorektal kanser tedavi stratejilerinin belirlenmesinde kullanılması mümkün olabilir. Bu konunun klinik pratiğe yansıtılması için daha ileri çalışmalara ihtiyaç vardır.Anahtar kelimeler: Kolon kanseri, S100A4, kalsiyum b...

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Overexpression of S100A4 is closely associated with progression of colorectal cancer

Abstract: Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.

Cited by 48 publications

References 17 publications

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

Prognostic value of cytoplasmic expression of S100A4 protein in endometrial carcinoma

Kolon Kanserinde S100A4 Ekspresyonunun Klinik ve Patolojik Önemi

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