Impact of Fibroblast-Derived SPARC on Invasiveness of Colorectal Cancer Cells

Drev, Daniel; Harpain, Felix; Beer, Andrea; Stift, Anton; Gruber, Elisabeth S.; Klimpfinger, M.; Thalhammer, Sabine; Réti, Andrea; Kenner, Lukas; Bergmann, Michael; Marian, Brigitte

doi:10.3390/cancers11101421

Cited by 21 publications

(15 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that JMJD5 was important for sustaining cell migration and invasion, and could be a potential oncogene for colon carcinogenesis [42]. SPARC is highly expressed in many tumors, and a research showed that its expression is related with metastasis and recurrence of colon cancer [43,44]. CTGF has shown to be associated with progression, tumorigenesis, and prognosis of various cancers [45,46].…”

Section: Discussionmentioning

confidence: 99%

WGCNA reveals key gene modules regulated by the combined treatment of colon cancer with PHY906 and CPT11

Xing

Wang

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

Irinotecan (CPT11) is one of the most effective drugs for treating colon cancer, but its severe side effects limit its application. Recently, a traditional Chinese herbal preparation, named PHY906, has been proved to be effective for improving therapeutic effect and reducing side effects of CPT11. The aim of this study was to provide novel insight to understand the molecular mechanism underlying PHY906-CPT11 intervention of colon cancer. Based on the GSE25192 dataset, for different three treatments (PHY906, CPT11, and PHY906-CPT11), we screened out differentially expressed genes (DEGs) and constructed a co-expression network by weighted gene co-expression network analysis (WGCNA) to identify hub genes. The key genes of the three treatments were obtained by merging the DEGs and hub genes. For the PHY906-CPT11 treatment, a total of 18 key genes including Eif4e, Prr15, Anxa2, Ddx5, Tardbp, Skint5, Prss12 and Hnrnpa3, were identified. The results of functional enrichment analysis indicated that the key genes associated with PHY906-CPT11 treatment were mainly enriched in “superoxide anion generation” and “complement and coagulation cascades”. Finally, we validated the key genes by GEPIA and RT-PCR analysis, the results indicated that EIF4E, PRR15, ANXA2, HNRNPA3, NCF1, C3AR1, PFDN2, RGS10, GNG11, and TMSB4X might play an important role in the treatment of colon cancer with PHY906-CPT11. In conclusion, a total of 18 key genes were identified in this study. These genes showed strong correlation with PHY906-CPT11 treatment in colon cancer, which may help elucidate the underlying molecular mechanism of PHY906-CPT11 treatment in colon cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

WGCNA reveals key gene modules regulated by the combined treatment of colon cancer with PHY906 and CPT11

Xing

Wang

et al. 2020

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“… 24 SPARC expression was decreased in PCa cell lines because of hypermethylation of the SPARC promoter, and SPARC hypermethylation was correlated with a poorer prognosis in PCa patients. 25 In colorectal cancer (CRC), high stromal SPARC indicated poor prognosis in CRC patients, and fibroblast-derived SPARC enhanced tumor cell invasion; 26 however, other studies revealed that low expression of SPARC in CRC tissue is associated with poor prognosis and aggressive clinicopathological features. 27 , 28 In studying the relationship between SPARC and gynecological tumors, we also found contradictory results.…”

Section: Discussionmentioning

confidence: 99%

<p>Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma</p>

Wang

2020

OTT

View full text Add to dashboard Cite

Background SPARC (secreted protein acidic and rich in cysteine), also known as osteonectin, BM-40, and 43 K protein, is a matricellular protein associated with various tumor progressions. The aim of this research was to investigate the prognostic value of SPARC in endometrial carcinoma (EC) and its function in cancer cell invasion and metastasis. Methods From both mRNA and protein levels, SPARC expression in normal endometrial tissue and EC tissue, normal endometrial cells and 4 EC cell lines (KLE, HEC-1A, HEC-1B, Ishikawa) were evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC), quantitative real-time PCR (qRT-PCR) and Western blotting. RNA interference mediated by lentivirus was performed to get the stable SPARC down-expressing cells. The functional analysis techniques in vitro and in vivo were used to detect the effects of SPARC knockdown on EC cell proliferation, apoptosis, invasion and metastasis. Results The expressions of SPARC in EC tissues and cells were much lower than those in normal endometrial cells and tissues; meanwhile, its low expression was closely related to the malignant clinicopathological characteristics of EC. SPARC knockdown could inhibit apoptosis, promote the process of EMT and improve the proliferation and invasion capacities of EC cells in vitro and in vivo. Conclusion The low expression of SPARC was detected in EC tissues and cells, which was positively correlated with the poor prognosis of EC patients. SPARC acted as a tumor suppressor gene that hindered EC progression, which proposed a new therapeutic strategy for EC treatment.

show abstract

“…The components of the desmoplastic stroma, such as type I collagen, have been described to enhance proliferation of PDAC cells [ 5 ], to increase invasion of tumor cells and to contribute to drug resistance by increasing expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) [ 6 , 7 ]. The tumor-promoting effects of the tumor stroma was not exclusively shown for PDAC, but also for other cancers, such as lung or colon cancer [ 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Diffusion Kurtosis Imaging—A Superior Approach to Assess Tumor–Stroma Ratio in Pancreatic Ductal Adenocarcinoma

Mayer

Jiang

Kuder

et al. 2020

Cancers

View full text Add to dashboard Cite

Extensive desmoplastic stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumor progression and to the relative resistance of tumor cells towards (radio) chemotherapy. Thus, therapies that target the stroma are under intense investigation. To allow the stratification of patients who would profit from such therapies, non-invasive methods assessing the stroma content in relation to tumor mass are required. In the current prospective study, we investigated the usefulness of diffusion-weighted magnetic resonance imaging (DW-MRI), a radiologic method that measures the random motion of water molecules in tissue, in the assessment of PDAC lesions, and more specifically in the desmoplastic tumor stroma. We made use of a sophisticated DW-MRI approach, the so-called diffusion kurtosis imaging (DKI), which possesses potential advantages over conventional and widely used monoexponential diffusion-weighted imaging analysis (cDWI). We found that the diffusion constant D from DKI is highly negatively correlated with the percentage of tumor stroma, the latter determined by histology. D performed significantly better than the widely used apparent diffusion coefficient (ADC) from cDWI in distinguishing stroma-rich (>50% stroma percentage) from stroma-poor tumors (≤50% stroma percentage). Moreover, we could prove the potential of the diffusion constant D as a clinically useful imaging parameter for the differentiation of PDAC-lesions from non-neoplastic pancreatic parenchyma. Therefore, the diffusion constant D from DKI could represent a valuable non-invasive imaging biomarker for assessment of stroma content in PDAC, which is applicable for the clinical diagnostic of PDAC.

show abstract

Impact of Fibroblast-Derived SPARC on Invasiveness of Colorectal Cancer Cells

Cited by 21 publications

References 47 publications

WGCNA reveals key gene modules regulated by the combined treatment of colon cancer with PHY906 and CPT11

WGCNA reveals key gene modules regulated by the combined treatment of colon cancer with PHY906 and CPT11

<p>Low Levels of SPARC are Associated with Tumor Progression and Poor Prognosis in Human Endometrial Carcinoma</p>

Diffusion Kurtosis Imaging—A Superior Approach to Assess Tumor–Stroma Ratio in Pancreatic Ductal Adenocarcinoma

Contact Info

Product

Resources

About