von Willebrand factor type D domain mutant of <i> SVS‐1/SUSD2</i>, vWD<sup>m</sup>, induces apoptosis in HeLa cells

Sugahara, Takuya; Yamashita, Yoshihisa; Shinomi, Masahito; Isobe, Yumiko; Yamanoha, Banri; Iseki, Hiroyoshi; Takeda, Akihiko; Okazaki, Yasushi; Kawai, Kenji; Suemizu, Hiroshi; Andoh, Toshiwo

doi:10.1111/j.1349-7006.2007.00467.x

Cited by 15 publications

(19 citation statements)

References 37 publications

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“…In our studies, analysis of the cellular localization of SUSD2 with fluorescent microscopy revealed a characteristic pattern of distribution in the cell-to-cell contact region. Our observation is in accordance with the [38,39]. A similar pattern of accumulation and biological activity of membrane proteins at cell-to-cell contact sites has also been reported in the case of other adhesion molecules, including E-cadherin, TSLC-1, and nectins [42][43][44][45].…”

Section: Discussionsupporting

confidence: 91%

“…Although the function of SUSD2 appears to be similar to that of a number of studied tumor suppressor molecules [38,39], the final assignment of this molecule as a tumor suppressor requires additional studies focusing on genetic/epigenetic alterations and abnormal expression patterns of SUSD2 in tumors. To get more insight into the biological functions of SUSD2 and to identify a potential extracellular ligand, cell-binding assays are in progress.…”

Section: Discussionmentioning

confidence: 98%

“…SUSD2 is a type I transmembrane protein of 820 amino acids that localizes in the plasma membrane [38]. Although the SUSD2 protein harbors several functional domains inherent to adhesion molecules, the biological role of SUSD2 remains to be clarified.…”

Section: Discussionmentioning

confidence: 99%

“…The function of the short cytoplasmic region of SUSD2 is not known. In a recent report, SUSD2 was described to be differentially expressed in skeletal muscle during the development of obesity [37] and to inhibit cellular growth and to reverse tumorigenic phenotypes of cancer cells in vitro [38,39]. The biological role and molecular mechanism of action of SUSD2 in tumor cells was investigated by analyzing the effect of SUSD2 overexpression in human HT1080 fibrosarcoma and in HeLa cervical carcinoma cells, which resulted in reduced or abrogated tumorigenic features such as the anchorage-independent growth, migratory and invasive activity of the cells [39].…”

Section: Introductionmentioning

confidence: 99%

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Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2

Sivasubramaniyan

Harichandan

Schumann

et al. 2013

Stem Cells and Development

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Several strategies have been developed to facilitate the prospective isolation of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) based on the selective expression or absence of surface markers. Recently, we described the monoclonal antibodies W3D5 and W5C5, which selectively react with BM-MSCs, but not with hematopoietic cells. Both antibodies showed an identical reactivity pattern, indicating that they may recognize the same molecule. To identify the cognate antigen, cultured MSCs were sorted for cells expressing either very high levels of W5C5/W3D5 antigen or for cells which were negative for this antigen. Further processing of these cells for microarray analysis revealed a 20-fold enrichment of the type 1 integral membrane protein Sushi domain containing 2 (SUSD2) in the in W5C5(+) subset. To confirm the identity of the W5C5/W3D5 antigen to SUSD2, HEK293 cells were transfected with the full-length coding sequence of human SUSD2 followed by reactivity analysis of W5C5 and W3D5 antibodies with the transfected line. Flow cytometric analysis showed that both antibodies selectively recognized HEK293/huSUSD2 cells, but not the parental cell line. In line with this, SUSD2 siRNA treatment of SUSD2(+) WERI-RB-1 retinoblastoma cells reduced the expression levels of W3D5 and W5C5 antigens to ~39% and 37%, respectively. Finally, FACSorting and colony assays revealed that only SUSD2(+), but not SUSD2(-) BM cells give rise to colony-forming units-fibroblasts and are able to differentiate into osteoblasts, adipocytes, and chondrocytes. In conclusion, we identified SUSD2 as a novel and specific marker for the prospective isolation of BM-MSCs.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2

Sivasubramaniyan

Harichandan

Schumann

et al. 2013

Stem Cells and Development

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“…Two studies by Sugahara et al (6,7) investigated the mouse homolog: SUSD2 (also known as mSVS-1 or SVS-1) was found to be downregulated in activated oncogene-v-K-ras-transformed NIH3T3 cells (Ki3T3 cells), compared with mouse NIH3T3 cells. One of the studies (6) revealed that overexpression of SUSD2 in HT1080 fibrosarcoma cells and HeLa cervical carcinoma cells inhibited clonogenicity, anchorage-independent growth, migration and invasion, via Matrigel assays.…”

Section: Introductionmentioning

confidence: 99%

Reduced expression of sushi domain containing 2 is associated with progression of non-small cell lung cancer

et al. 2015

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Abstract. Sushi domain containing 2 (SUSD2) has been identified as a gene encoding an 822-amino acid protein, which contains a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies have reported that increased expression of SUSD2 has a critical role in tumorigenesis in human breast cancer. However, to the best of our knowledge, SUSD2 expression status and its correlation with the clinicopathological features of non-small cell lung cancer (NSCLC) have not previously been investigated. In the present study, reverse transcription-quantitative polymerase chain reaction and western blotting were used to evaluate SUSD2 messenger RNA (mRNA) and protein expression in NSCLC and adjacent normal lung tissues. The clinicopathological significance of SUSD2 was investigated by immunohistochemical analysis of an NSCLC tissue microarray. Receiver operating characteristic analysis was used to determine the cut-off score for positive expression of SUSD2. Furthermore, the correlation between SUSD2 expression and the clinicopathological features of NSCLC was analyzed by χ 2 test. The results revealed that SUSD2 mRNA (P<0.0001) and protein (P<0.0001) expression levels were significantly decreased in NSCLC tissues compared with those of adjacent normal tissues. When the SUSD2 positive expression percentage was determined to be >47.5% (area under ROC curve, 0.799; P<0.000), positive expression of SUSD2 was observed in 100% (32/32) of normal lung tissues and 55% (88/160) of NSCLC tissues by immunohistochemistry (χ 2 =21.160; P<0.000). Furthermore, it was demonstrated that the reduced SUSD2 protein levels in cancer tissues were positively correlated with poor histological grade (χ 2 =41.764; P<0.000), advanced clinical stage (χ 2 =10.790; P=0.013), higher pT (χ 2 =9.070; P=0.028) and positive regional lymph node metastasis (χ 2 =15.399; P=0.002).In conclusion, these data suggest that the reduced expression of SUSD2 is associated with the progression of NSCLC and may have a role in the pathogenesis of NSCLC.

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SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer

Cheng

Wang

et al. 2016

Tumor Biol.

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Sushi domain containing 2 (SUSD2) is type I membrane protein containing domains inherent to adhesion molecules. There have been few reported studies on SUSD2, and they have mainly focused on breast cancer, colon cancer, and HeLa cells. However, the expression and function of SUSD2 in other cancers remain unclear. In the present study, we conducted an integrated bioinformatics analysis based on the array data from the GEO database and found a significant downregulation of SUSD2 in renal cell carcinoma (RCC) and lung cancer. Western blotting and quantitative RT-PCR (qRT-PCR) confirmed that SUSD2 was frequently decreased in RCC and lung cancer tissues compared with the corresponding levels in normal adjacent tissues. The restoration of SUSD2 expression inhibited the proliferation and clonogenicity of RCC and lung cancer cells, whereas the knockdown of SUSD2 promoted A549 cell growth. Our findings suggested that SUSD2 functions as a tumor suppressor gene (TSG) in RCC and lung cancer.

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von Willebrand factor type D domain mutant of SVS‐1/SUSD2, vWD^m, induces apoptosis in HeLa cells

Abstract: SVS-1/SUSD2 is a novel gene, which inhibits growth and reverses

Cited by 15 publications

References 37 publications

Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2

Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2

Reduced expression of sushi domain containing 2 is associated with progression of non-small cell lung cancer

SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer

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von Willebrand factor type D domain mutant of SVS‐1/SUSD2, vWDm, induces apoptosis in HeLa cells

Abstract: SVS-1/SUSD2 is a novel gene, which inhibits growth and reverses

Cited by 15 publications

References 37 publications

Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2

Prospective Isolation of Mesenchymal Stem Cells from Human Bone Marrow Using Novel Antibodies Directed Against Sushi Domain Containing 2

Reduced expression of sushi domain containing 2 is associated with progression of non-small cell lung cancer

SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer

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von Willebrand factor type D domain mutant of SVS‐1/SUSD2, vWD^m, induces apoptosis in HeLa cells