Detection of cd43 (leukosialin) in colon adenoma and adenocarcinoma by novel monoclonal antibodies against its intracellular domain

Sikut, Rein; Andersson, Christian X.; Sikut, Anu; Fernández-Rodrı́guez, Julia; Karlsson, Niclas G.; Hansson, Gunnar C.

doi:10.1002/(sici)1097-0215(19990702)82:1<52::aid-ijc10>3.0.co;2-c

Cited by 24 publications

(22 citation statements)

References 19 publications

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“…One reason for CD43 being unnoticed outside of the hematopoietic lineage is that CD43 is differently glycosylated in other cells, as, for example, the human colon adenocarcinoma COLO205 cells (Baeckstrom et al, 1991). Moreover, in colon adenoma and carcinoma tissues, CD43 seems to have a more intracellular localization, in contrast to the membrane localization typical for leukocyte-type cells (Sikut et al, 1999).…”

Section: Introductionmentioning

confidence: 76%

“…For flow cytometry analysis, approximately 10 6 cells were washed with PBS, fixed in methanol at À201C for 15 min and permeabilized in 0.1 % saponin solution on ice for 30 min. The anti-CD43 antibody 4D2 (Sikut et al, 1999) was added to the cells followed by incubation on ice for 45 min. Biotinconjugated goat anti-mouse secondary antibody (Dako) was used, diluted 1 : 200 and incubated on ice for 45 min followed by streptavidin-APC substrate (Perkin-Elmer).…”

Section: Protein Analysismentioning

confidence: 99%

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Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor proteins p53 and ARF

2003

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CD43 or leukosialin is a transmembrane sialoglycoprotein, whose extracellular domain participates in cell adhesiveness and the cytoplasmic tail regulates a variety of intracellular signal transduction pathways involved in cell proliferation. CD43 is abundantly expressed on the surface of hematopoietic cells, but CD43 expression is also frequently found in the tumor cells of nonhematopoietic origin. In the early stages of some tumors, the accumulation of tumor suppressor protein p53 has been described. Here, we show that the expression of CD43 causes the induction of functionally active p53 protein.Moreover, we found that the activation of p53 by CD43 is mediated by tumor suppressor protein ARF. The coexpression of CD43 and ARF in ARF-null mouse embryonic fibroblasts resulted in programmed cell death, but that was not the case when CD43 alone was expressed in these cells. These data provide the first evidence of the connection between p53-and CD43-dependent pathways.

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Section: Introductionmentioning

confidence: 76%

Section: Protein Analysismentioning

confidence: 99%

Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor proteins p53 and ARF

2003

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“…16,23,[25][26][27][28]37,39,40 While CD43 is normally restricted in its expression to leukocytes and platelets, aberrant expression has been consistently described in colon and salivary gland cancers. [41][42][43][44] In addition, limited analysis suggested that NSCLC but not SCLC might also be characterized by CD43 expression. 2,3 Using the anti-CD43 antibodies L10 and SSGZ together with extensive patient samples we have determined that CD43 is frequently expressed not only by NSCLC but also by SCLC.…”

Section: Discussionmentioning

confidence: 99%

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target

Cash

Andersen

et al. 2012

Intl Journal of Cancer

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CD43 is a transmembrane sialoglycoprotein. Normally the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signaling, apoptosis, migration and proliferation. Two CD43 antibodies were used to interrogate 66 cases of non-small cell lung cancer (NSCLC) and 24 cases of small cell lung cancer (SCLC). In addition, we engineered the CD43-positive lung cancer cell line A549 to stably express either non-targeted or CD43-targeted small-interfering RNA (siRNA). These lines were then subjected to in vitro assays of apoptosis, natural killer (NK) cell cytotoxicity, intercellular adhesion and transendothelial migration. A xenograft mouse model evaluated the ability of the lines to grow primary tumors in vivo. CD43 was found to be expressed in the majority of both SCLC and NSCLC. Inclusive of CD43-negative tumors, differential patterns of nuclear and cytoplasmic expression of CD43 define four molecular subcategories of lung cancer. Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells. Furthermore, targeting inhibited the growth of primary tumors in nude mice.Despite major advances in the field of medical oncology, lung cancer remains the leading cause of cancer death in the United States among both men and women. With an estimated 221,130 new cases and 156,940 deaths in 2011, lung cancer is responsible for more than 25% of all cancer deaths. 1 Two studies have reported that lung cancer might be characterized by expression of the sialoglycoprotein CD43 normally only produced by leukocytes. 2,3 The first study reported that 13 out of 13 cases of non-small cell lung cancer (NSCLC) expressed CD43 while two out of two cases of small cell lung cancer (SCLC) were CD43-negative. 2 The second study reported that one out of three primary lung tumors exhibited CD43 expression. 3 One of these three tumors was a smallcell carcinoma and the other two were squamous cell carcinomas. Here, we report the analysis of 90 cases of lung cancer using antibodies that recognize either the N or C terminus of CD43. In addition, we report the functional consequences of expressing CD43-targeted small-interfering RNA (siRNA) in the lung cancer cell line A549. Material and Methods Patient materialParaffin-embedded formalin-fixed tissues representing 90 cases of lung cancer and one mild case of lung silicosis were provided free-of-charge by the Gundersen Foundation BioBank (http://www.gundluth.org/biobank). Each case was sectioned, stained with hematoxylin and eosin and the histological diagnosis verified. All experimental procedures were

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“…In colonic epithelial cells, carrier proteins of ligands for CD22 and sialoadhesin are 54-, 49-, and 44-kDa glycoproteins. These sialoglycoproteins are unlike epithelial mucins, which are larger glycoproteins (Ͼ200 kDa), but like CD43 (Sikut et al, 1999). In endothelial cells, a 60-kDa sialoglycoprotein is a major carrier protein of ligands for CD22 and sialoadhesin.…”

Section: Cao Et Almentioning

confidence: 99%

Differential Expression of β-Galactoside α2,6 Sialyltransferase and Sialoglycans in Normal and Cirrhotic Liver and Hepatocellular Carcinoma

Cao

Merling

Crocker

et al. 2002

Laboratory Investigation

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SUMMARY:Sialyltransferases sialylate plasma glycoproteins in hepatocytes and may (as hepatic key enzymes) constitute markers for liver diseases. We examined expression of the prevalent ␣2,6 sialyltransferase (ST6Gal I) and sialoglycans in normal liver, cirrhotic liver, and hepatocellular carcinoma (HCC) using a new ST6Gal I-specific mAb and recombinant fusion proteins of CD22 and sialoadhesin recognizing ␣2,6-or ␣2,3-sialylated glycans in immunohistology and flow cytometry. In normal and cirrhotic liver, ST6Gal I and sialoglycans were localized in the Golgi region of hepatocytes surrounding the bile canaliculi and along the bile canaliculi, respectively. Sialoglycans were additionally recognized in Kupffer cells, bile ducts, endothelial cells, and oval cells. Well-differentiated and moderately differentiated HCC showed Golgi and diffuse cytoplasmic staining of ST6Gal I and sialoglycans, whereas the cytoplasmic staining for ST6Gal I and sialoglycans was decreased or even absent in poorly differentiated HCC. Detection of sialoglycans by the recombinant fusion proteins in Western blots of cell lysates derived from cell lines revealed two major double bands of sialoglycoproteins at 65 and 120 kDa for hepatocytes, three major bands at 54, 49, and 44 kDa for colonic epithelial cells, and one band at 60 kDa for endothelial cells. Our results describe the expression patterns of ST6Gal I and sialoglycans in various liver tissues and demonstrate an altered expression of these structures between benign and malignant hepatocellular lesions. (Lab Invest 2002, 82:1515-1524.

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Detection of cd43 (leukosialin) in colon adenoma and adenocarcinoma by novel monoclonal antibodies against its intracellular domain

Cited by 24 publications

References 19 publications

Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor proteins p53 and ARF

Overexpression of leukocyte marker CD43 causes activation of the tumor suppressor proteins p53 and ARF

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target

Differential Expression of β-Galactoside α2,6 Sialyltransferase and Sialoglycans in Normal and Cirrhotic Liver and Hepatocellular Carcinoma

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