Expression and Regulation of CD97 in Colorectal Carcinoma Cell Lines and Tumor Tissues

Steinert, M.; Wobus, Manja; Boltze, Carsten; Schütz, Alexander; Wahlbuhl, Mandy; Hamann, Jörg; Aust, Gabriela

doi:10.1016/s0002-9440(10)64443-4

Cited by 119 publications

(159 citation statements)

References 40 publications

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“…Na butyrate has been used as an inhibitor of proliferation in the MDA-MB-231 cells [50,51]. Na butyrate inhibits histone deacetylase, increases p21 expression, and decreases cyclin D gene expression [50] resulting in an arrest of the cell in G2 [51].…”

Section: Discussionmentioning

confidence: 99%

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Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

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Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1-50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified "checkerboard" analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1.

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Section: Discussionmentioning

confidence: 99%

“…Na butyrate inhibits histone deacetylase, increases p21 expression, and decreases cyclin D gene expression [50] resulting in an arrest of the cell in G2 [51]. Na butyrate also induces cell differentiation [50], as shown with an increase in lipid accumulation, and a reduction in migration across multiple extracellular matrices [52].…”

Section: Discussionmentioning

confidence: 99%

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Beaulieu

Church

2007

Experimental Cell Research

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“…CD97 levels correlate with the in vitro migration and invasion capacity of colorectal tumor cell lines and CD97-transfected cells. 6 Colorectal carcinomas with more strongly CD97-stained, scattered tumor cells at the invasion front showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. 6 In thyroid cancers, CD97 expression parallels the aggressiveness and lymph node involvement of these tumors.…”

mentioning

confidence: 88%

N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding

Wobus

Vogel

Schmücking

et al. 2004

Intl Journal of Cancer

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CD97 is an EGF-TM7 receptor found on various carcinomas where expression levels correlate with dedifferentiation and tumor stage, smooth muscle cells and leukocytes. CD97 acts as an adhesion molecule by binding to its cellular ligand, CD55. In this study, we demonstrate that 2 immunodominant CD97 epitopes are not equally present in the various cell types. Differences were apparent in gastrointestinal tumors and smooth muscle cells where monoclonal antibodies (mAbs) to the first epidermal growth factor (EGF) domain (CD97 EGF ) showed a more restricted staining pattern than mAbs to the stalk region (CD97 stalk ). This discrepancy was not detectable in cultured gastrointestinal tumor cell lines. In fact, the selection of the CD97 mAb influences the result of clinical studies. Thus, we clarified the reason(s) for these differences in CD97 mAb staining on various cell types. We provide evidence that epitope accessibility for CD97 EGF Key words: CD97; colorectal cancer; smooth muscle cell; epitope accessibility; glycosylation CD97 is a member of a subfamily of 7-span transmembrane (TM7) receptors referred to as EGF-TM7 proteins. 1,2 In normal tissues, CD97 is abundantly expressed in smooth muscle cells, macrophages, granulocytes, dendritic cells and in some T and B cells. 3 Carcinomas of different origin showed higher CD97 expression compared to the corresponding normal cell types. 4 -7 CD97 consists of an extended extracellular region with several N-terminal epidermal growth factor (EGF) domains coupled to the TM7 domain by a stalk. 1,8 Various CD97 isoforms exist possessing 3 (EGF 1,2,5), 4 (EGF 1,2,3,5), or 5 (EGF 1,2,3,4,5) EGF domains. CD97 binds to membrane receptor CD55. 9 This interaction is mediated by the first 2 CD97 EGF domains. 9 -11 Chondroitin sulfate glycosaminoglycan, present in cell membranes and the extracellular matrix, is a new ligand to the longest CD97 isoform (EGF 1,2,3,4,5). 12 The ability of CD97 EGF domains to interact with cellular and/or extracellular matrix ligands suggests that the molecule is involved in cell-cell or cell-matrix interactions. Various lines of evidence have shown an important role for CD97 in tumor dedifferentiation, migration, invasiveness and metastasis. CD97 levels correlate with the in vitro migration and invasion capacity of colorectal tumor cell lines and CD97-transfected cells. 6 Colorectal carcinomas with more strongly CD97-stained, scattered tumor cells at the invasion front showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. 6 In thyroid cancers, CD97 expression parallels the aggressiveness and lymph node involvement of these tumors. 4,5 Our previous data revealed that CD97 has prognostic and therapeutic potential in cancer. However, analyzing CD97 expression brings up the phenomenon that different staining patterns, depending on which CD97 monoclonal antibody (mAb) has been used for immunohistology, can be readily observed in pancreatic tissues. 7,13 Based on this observation, one aim of ...

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“…All leiomyomas and 9 out of 21 leiomyosarcomas were CD97 positive . The disability of muscular CD97 to bind the ligand CD55 implicates another function in this cell type (Wobus et al, 2004) as the suggested role as an adhesion molecule (Hamann et al, 1996) in tumor cells where CD97 promotes migration capacity (Galle et al, 2006;Steinert et al 2002). Based on these findings, we are eminently interested in CD97 regulatory mechanisms in SMCs.…”

Section: Introductionmentioning

confidence: 94%

“…We described CD97 expression in cells of the hematopoetic system and detected CD97 overexpression in tumor cells of different origin Steinert et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle cells

Wobus

Wandel

Prohaska

et al. 2008

Gene

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The EGF-TM7 receptor CD97 shows different features of expression and function in muscle cells compared to hematopoetic and tumor cells. Since the molecular function and regulation of CD97 is poorly understood, this study aimed at defining its basal transcriptional regulation in smooth muscle cells (SMCs).The computational analysis of the CD97 5'-flanking region revealed that the TATA boxlacking promoter possesses several GC-rich regions as putative Sp1/Sp3 binding sites.Transfection studies with serially deleted promoter constructs demonstrated that the minimal promoter fragment resided in the -218/+45 region containing one out of five identified GCboxes in the leiomyosarcoma cell line SK-LMS-1 and human bronchial smooth muscle cells (HbSMCs). Mutation of the most proximal GC-site in CD97 reporter gene constructs caused a significant decrease in promoter activity. Gel shift assays and chromatin immunoprecipitation revealed that Sp1 and Sp3 bound specifically to the most proximal GC-site. Furthermore, we showed that Sp1 and Sp3 over-expression activates CD97 promoter activity in HEK 293 cells.Our data characterize for the first time the activity of the human CD97 promoter which is controlled by Sp1/Sp3 transcription factors in SMCs.2

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Expression and Regulation of CD97 in Colorectal Carcinoma Cell Lines and Tumor Tissues

Cited by 119 publications

References 40 publications

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

N‐glycosylation of CD97 within the EGF domains is crucial for epitope accessibility in normal and malignant cells as well as CD55 ligand binding

Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle cells

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