Cd44 and Splice Variants of Cd44 in Normal Differentiation and Tumor Progression

Herrlich, Peter; Rudy, Wolfgang; Hofmann, Martin; Arch, Robert H.; Zöller, Margot; Zawadzki, Volker; Tölg, Cornelia; Hekele, Armin; Koopman, Gerrit; Pals, Steven T.; Heider, Karl-Heinz; Sleeman, Jonathan P.; Ponta, Helmut

doi:10.1007/978-1-4615-2830-2_17

Cited by 16 publications

(7 citation statements)

References 28 publications

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“…However, using the expression of different CK as markers for cellular differentiation we found a higher incidence of CK8 and 20 expression in CD44-negative gastrointestinal neuroendocrine neoplasms than in CD44-positive ones, and the opposite was true for pancreatic neuroendocrine tumors. Thus, it may be speculated that, similar to other human carcinoma types, a tissue-and tumor-type dependent relationship between CD44 expression and cellular differentiation exists (Herrlich et al 1993a;Sherman et al 1994Sherman et al , 1996Friedrichs et al 1995;Ghaffari et al 1995;Hong et al 1995;Seelentag et al 1996b) and that CD44 isoforms are useful additional markers of differentiation in neuroendocrine tumors.…”

Section: Discussionmentioning

confidence: 96%

CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and malignant tumors

Komminoth

Seelentag

Saremaslani

et al. 1996

Histochem Cell Biol

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The membrane glycoprotein CD44 may be associated with aggressive behavior, dissemination, and poor prognosis of a variety of human tumors. In order to extend our knowledge on the expression and significance of CD44 in cells of the dispersed neuroendocrine system we investigated a spectrum of 134 neuroendocrine tumors, including pituitary adenomas, medullary thyroid carcinomas, parathyroid adenomas, pheochromocytomas, neuroblastomas, small-cell lung carcinomas, and bronchopulmonary, pancreatic, and gastrointestinal neuroendocrine tumors immunohistochemically for CD44 standard and variant exon-encoded gene products (CD44v3, -v4, -v5, -v6, -v9). Furthermore, we compared protein expression with that of CD44 mRNA by reverse-transcriptase PCR and Southern blot hybridization in a subset of tumors. Our results show that CD44 expression is correlated with the "histogenetic origin" of the appropriate neuroendocrine neoplasm. Endoderm-derived tumors generally express 3'-end CD44 variant exon-containing isoforms, whereas neural crest-derived tumors rarely are positive for CD44. Furthermore, we provide evidence that CD44 expression is not correlated with metastatic disease or a particular hormonal phenotype but exhibits an association with the degree of cellular differentiation. Thus, CD44 is not useful as marker for malignancy or prognosis. The number of patients with clinical follow-up data in our study was too small to allow definite conclusions about a possible correlation between CD44 expression and prognosis. But CD44 may help to better classify neoplasms with an unclear neuroendocrine phenotype.

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Section: Discussionmentioning

confidence: 96%

CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and malignant tumors

Komminoth

Seelentag

Saremaslani

et al. 1996

Histochem Cell Biol

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“…The conserved AP-1 binding site at position Ϫ110 to Ϫ104 mediates an increase in CD44 promoter activity after transformation of rat embryo fibroblasts by ras, which is consistent with the role of CD44 in tumor progression and metastasis (53). This AP-1 site has also been suggested to mediate CD44 promoter induction by phorbol esters (64). The invasive potential of fibroblasts transformed by epidermal growth factor and/or oncogenic fos requires AP-1-mediated induction of CD44 (65).…”

Section: Discussionmentioning

confidence: 97%

Role of activating protein‐1 and high mobility group‐I(Y) protein in the induction of CD44 gene expression by interleukin‐1β in vascular smooth muscle cells

et al. 2000

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CD44 is a multifunctional cell adhesion molecule that participates in pathological states such as inflammation and tumorigenesis. CD44 is induced on vascular smooth muscle cells after arterial wall injury and may mediate their proliferation and migration into the neointima during arteriosclerosis. We have demonstrated elsewhere that the proinflammatory cytokine interleukin (IL)-1beta up-regulates CD44 mRNA and protein expression in cultured rat aortic smooth muscle cells (RASMC) by increasing gene transcription. By transient transfection of 5'-deletion constructs into RASMC, we show in the present study that a conserved AP-1 site 110 base pairs from the transcription start site of the mouse CD44 promoter is important for basal activity. Mutation of the AP-1 site significantly reduced induction of promoter activity by IL-1beta, and electrophoretic mobility shift assays demonstrated that Fos and c-Jun were present in the CD44 AP-1 binding complex after IL-1beta stimulation. In addition, cotransfection of the architectural transcription factor high mobility group (HMG)-I(Y) protein with c-Fos and c-Jun markedly increased trans-activation of the CD44 promoter. Taken together, our studies demonstrate that AP-1 proteins are a central regulatory component used by IL-1beta to modulate expression of CD44 during an inflammatory response in vascular smooth muscle cells and that transcription of CD44 by AP-1 proteins is enhanced by HMG-I(Y). -Foster, L. C., Wiesel, P., Huggins, G. S, Pañares, R., Chin, M. T., Pellacani, A., Perrella, M. A. Role of activating protein-1 and high mobility group-I(Y) protein in the induction of CD44 gene expression by interleukin-1beta in vascular smooth muscle cells.

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“…The observation that the CD44std protein continued to be present at the membrane in high-grade SILs and invasive SCC to a larger extent than that seen with Ecadherin may be due to (1) CD44 being the principal cell surface receptor for hyaluronic acid and other extracellular matrix molecules as collagen and fibronectin [37,38], and (2) the CD44 protein acting as a molecular disguise, helping tumor cells to appear like normal lymphocytes, and managing in this way to escape the immune surveillance system and perform cell-to-cell and cell-matrix interactions necessary for metastatic spread, since the CD44 molecule at the surface of lymphocytes mediate entry into high endothelial venules, and thus allow entry into lymphatic tissue [8,39], and (3) CD44 playing a crucial role in cell-to-cell and cell-extracellular matrix adhesion in tissue specific pathways used in inflammation, tissue regeneration, T cell activation, cell migration and in cell proliferation [33,39].…”

Section: Discussionmentioning

confidence: 99%

“…It is known that E-cadherin, CD44 and CD44 variant isoforms are involved in various biological events as cellto-cell and cell-matrix adhesive interactions, and that the impairment of these molecules are likely to contribute to the reduced cell-cell adhesion characteristic of tumor cells [8,15,16].…”

Section: Discussionmentioning

confidence: 99%

“…The smallest form of CD44 is the standard CD44 (CD44std), which does not contain any of the variant exons. CD44 proteins have been implicated in a diverse range of functions with numerous important and separate cellular activities such as cellular migration, proliferation, cell-to-cell and cellmatrix adhesion, lymphocyte homing and activation [8].…”

Section: Introductionmentioning

confidence: 99%

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E-Cadherin, CD44 and CD44v6 in Squamous Intraepithelial Lesions and Invasive Carcinomas of the Uterine Cervix: An Immunohistochemical Study

Faleiro-Rodrigues

Lopes

2004

Pathobiology

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Objective: To evaluate the immunoexpression pattern of E-cadherin, CD44std and the variant isoform v6 in normal squamous epithelium, low and high squamous intraepithelial lesions (SILs) and invasive squamous cell carcinomas (ISCCs) of the uterine cervix. The purpose was to determine whether any distinctive change in antigenic expression could contribute to the recognition of the earliest commitment to neoplasia and/or the onset of the invasive phenotype. Methods: Immunohistochemistry using the avidin-biotin indirect immunoperoxidase method was used to study the protein expression of epithelial cadherin (E-cadherin), cluster differentiation 44 (CD44), and the isoform v6 (CD44v6) in 124 human cervical samples (5 normal, 39 low-grade, 54 high-grade and 26 ISCCS) in formalin-fixed, paraffin-embedded tissue blocks. Results: Membranous expression of E-cadherin, CD44 and CD44v6 was preserved in normal squamous epithelium and in low-grade squamous intraepithelial lesions. A significant association was observed with the histological grade of the SILs and the immunoreactivity (membranous versus cytoplasmic) pattern of E-cadherin (p < 0.001), CD44std (p = 0.027) and CD44v6 (p < 0.001). A loss of membranous staining and a progressive increase in cytoplasmic staining was observed from low to high grade SILs to ISCCs. Conclusions: Our study demonstrates that during the development of cervical lesions substantial qualitative (subcellular localization-membrane to cytoplasmic) and quantitative alterations (changes in expression) occur in the protein expression of E-cadherin, CD44, and CD44v6 in cervical cancer. The most striking observation was the decrease in membranous immunoreactivity and the progressive increase in cytoplasmic staining of E-cadherin, CD44 and CD44v6, relating to loss of differentiation as a consequence of neoplastic transformation.

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Cd44 and Splice Variants of Cd44 in Normal Differentiation and Tumor Progression

Cited by 16 publications

References 28 publications

CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and malignant tumors

CD44 isoform expression in the diffuse neuroendocrine system. II. Benign and malignant tumors

Role of activating protein‐1 and high mobility group‐I(Y) protein in the induction of CD44 gene expression by interleukin‐1β in vascular smooth muscle cells

E-Cadherin, CD44 and CD44v6 in Squamous Intraepithelial Lesions and Invasive Carcinomas of the Uterine Cervix: An Immunohistochemical Study

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