Sandbox Reserved 954

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This Sandbox is Reserved from 15/11/2014, through 15/05/2015 for use in the course "Biomolecule" taught by Bruno Kieffer at the Strasbourg University. This reservation includes Sandbox Reserved 951 through Sandbox Reserved 975.
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Contents

Squamous cell carcinoma antigen 1

This is a default text for your page '. Click above on edit this page' to modify. Be careful with the < and > signs. You may include any references to papers as in: the use of JSmol in Proteopedia [1] or to the article describing Jmol [2] to the rescue.

Introduction

Squamous cell carcinoma antigen is a tumor associated protein of squamous cell carcinoma of various organs. SCCA was originally purified from SCC of the uterine cervix [3]. SCCA is a tumor marker to detect malignant tumor and to understand biological behaviors of squamous cells. SCCA is classified as a serine protease inhibitor called serpin B3. It also inhibits chymotrypsin and cathepsin L, papain like cysteine proteases. In the case of tumor development SCCA 1 inhibits, NK (natural killer), TNFalfa and apoptosis of tumor cells induced by treatment. It can also play a role in tumor growth. The chromosomal location is the locus 18q21.3.[4]

Structure

The SCCA1 a tumor marker

Cancer is characterize as the abnormal proliferation of a cellular clone it will conduce to form a tumor in tissue. Tumoral cells can migrate to the serum or urin and invade other tissue. Cancer is caused by damaged genes. The cancer can have several origins exogenous factors (cigarettes, alcohol, UV) or endogenous factors (failure DNA repair). Tumor markers are substances present in abnormal concentration in serum or urine in patients who develop a malignant tumor. Nevertheless tumor markers can appear in people who don’t suffer from cancer or be low for sick patients, this is the false negative or false positive. Tumor markers are used to detect, prevent, diagnose, predict, determine, prognostic and therapeutic monitoring. Tumor markers need to be specific and sensible. The dosage of several markers is necessary to establish the success or the fail of treatment.

The SCCA is secreted by the tumor itself, it a marker of mature cells. It is included in the antigen associated to tumor.The SCCA is a glycoprotein present in the epithelium and release in the serum during epidermoid cervical cancer but also in epidermoid cancers as lung, mouth, larynx, pharynx and esophagus. The threshold is inferior at 1.5 µg/L. P. Kerbrat [5]

SCCA role as a tumor marker

SCCA is particularly used for cancer of the uterine cervix. The correlation between SCCA concentration and lung tumor was proved. SCCA concentration increase with the presence of epidermoid lung tumor, independently of the differentiation state of the tumor[6]. SCCA is especially used to prognostic and follow the effects of the treatment in the lung cancer as second tumor marker [7] . High concentration of SCCA in the blood suggests the epithelial cells direct serpin activity to blood. This pathway is an active secretory process[8].

SCCA and cancer

SCCA is not specific of one type of cancer. It can be associated to mild bronchopulmonarypathology, mild skin pathology. It doesn’t depend on Tabaco consumption. SCCA is associated to cancer and non malignant kidney pathology. It is dosed par immune-analyzes. Its half-life is 3 days.

-In cervix cancer : The SCCA augmentation is linked to the tumor weight and state of disease. Nevertheless 40 % of patients suffer from cervix cancer have a high SCCA blood concentration, it is not use for screening. An increase of initial rate can be a sign of disease recurrence or persistence. It allows to follow the treatment efficiency in patients such as chemotherapy, radiotherapy.

-In epidermoid bronchopulmonary cancer : SCCA is not used for screening, it is more specific. [9]

Interaction

Hepatite B virus (HBV) interaction

The SCCA may have a role of cellular receptor for hepatitis B virus. The SCCA expression enhances the binding and internalization of hepatitis B virus with hepatocyte or non-hepatocytes origin cells. The transfection of SSCA in hepatocyte generates more viruses DNA in infected cells. Besides the virus bound to transfected cell is protected against degradation by trypsin thanks to a partial internalization. The binding between HBV and hepatocytes is more marked than for the others types of cells like the cells COS-7 (kidney cells of monkey transformed by antibody T of SV40) in this experiment. The binding complex of cells COS-7 with HBV seems to be more complex and may need one more binds. The low density lipoprotein receptor-related protein (LRP) mediates the clearance of serpin-enzyme complex, the LRP may not enhanced virus binding to transfected cells. SCCA may be a co-receptor for HBV, virus binding to the transfected cells doesn’t depend on the proteinase inhibitor function or the interaction receptor LRP but it may depend on the reactive site loop of SCCA. [10]

Receptor (LPR) interaction

The serpin and serpin-protease complexes are able to link the low density lipoprotein receptor-related protein (LPR). This binding allow to clear serpin- complexes from circulation. The ligand bind a clusters of rich cysteine residu complement like repeats. No differences were noticed between native and cleaved serpin. The binding between serpin and enzyme such as protease may increase the affinity of the complexe for LPR [11]

Disease

Asthma is characterized by an obstruction of the interior respiratory tract and an excessive mucus secretion.[12] Experiments were performed on mice, mice lacking SerpinB3 showed a decrease of the mucus secretion. As a result serpinB3 may have a role in mucus hypersecretion in a house dust mit model of asthma. The SPDEF ( SAM pointed domain containing ETS transcription factor) expression causes the hyperplasia of goblet cell. The hyperplasia designates the abnormal augmentation of cells number in a tissue, the subexpression of goblet cells m ay induce cancer. Serpin B3 increase SPDEF expression and goblet cells hyperplasia. [13]

Regulation

The E-cadherin can regulate the SCCA production in the squamous cell carcinoma of the uterin cervix. E-cadherin are transmembrane protein, they have a role in cell adhesion because they are able to form adherens junctions. They have to link a Ca++ ion to function. Using an anti-E-cadherin antibody conduces to dissociate the cervical squamous cell carcinoma. It also induces decrease of SCCA in the cytosol and SCCA m RNA. Besides the phosphatidyl inositol 3 kinase is a mediator of E-cadherin. The E-cadherin mediated cell-cell adhesion and maintains SCCA production thanks to phosphatidyl inositol 3 kinase in squamous cell carcinoma.[14]

Structural highlights

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References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ Martz, E. Book review of Introduction to protein science—architecture, function, and genomics: Lesk, Arthur M. Biochem. Mol. Biol. Educ. 33:144-5 (2006). DOI :10.1007/978-1-4612-0401-5_21#page-1
  4. ↑ Suminami Y, Nawata S, Kato H. Biological role of SCC antigen. Tumour Biol. 1998;19(6):488-93. PMID:9817978
  5. ↑ Que faire des marqueurs tumoraux, Centre Eugène Marquis, Université de Rennes 1 DOI : stock/RENNES20110504094607cpiszkormarqueurs_tumoraux.coursDCEM1-02-2011.pdf
  6. ↑ Upham J, Campbell B. Utility of squamous cell carcinoma antigen (SCC Ag) as a tumour marker in pulmonary malignancy. Respir Med. 1992 May;86(3):201-3. PMID:1620906
  7. ↑ Les marqueurs tumoraux Tableau d’aide à la description des principaux marqueurs tumoraux, Ketterhill laboratoires d’analyses médicales DOI : newsletter/Marqueurs_Tum.pdf
  8. ↑ Uemura Y, Pak SC, Luke C, Cataltepe S, Tsu C, Schick C, Kamachi Y, Pomeroy SL, Perlmutter DH, Silverman GA. Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells. Int J Cancer. 2000 Jul 20;89(4):368-77. PMID:10956412
  9. ↑ Micke O, Prott FJ, Schäfer U, Tangerding S, Pötter R, Willich N.The impact of squamous cell carcinoma (SCC) antigen in the follow-up after radiotherapy in patients with cervical cancer. Anticancer Res 2000 ; 20 : 5113-5115. National Academy of Clinical Biochemistry.Guidelines for the Use of Tumor Markers in cervical cancer.[//www.nacb.org/lmpg/tumor/chp3j_cervical.d DOI : tumor/chp3j_cervical.d]
  10. ↑ Penelope L. Moore‡, Sarah Ong, and Tim J. Harrison§, Squamous Cell Carcinoma Antigen 1-mediated Binding of Hepatitis B Virus to Hepatocytes Does Not Involve the Hepatic Serpin Clearance System*DOI 47/46709.full
  11. ↑ PMID: PMC2709341
  12. ↑ Santé médecine, Hyperplasie définitionDOI : faq/13479-hyperplasie-definition
  13. ↑ Morse GD, Holdsworth MT, Venuto RC, Gerbasi J, Walshe JJ. Pharmacokinetics and clinical tolerance of intravenous and oral cyclosporine in the immediate postoperative period. Clin Pharmacol Ther. 1988 Dec;44(6):654-64. PMID:3058372
  14. ↑ Hirakawa H, Nawata S, Sueoka K, Murakami A, Takeda O, Numa F, Kato H, Sugino N. Regulation of squamous cell carcinoma antigen production by E-cadherin mediated cell-cell adhesion in squamous cell carcinoma cell line. Oncol Rep. 2004 Feb;11(2):415-9. PMID:14719077
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