Sandbox Reserved 954
From Proteopedia
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==Introduction== | ==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 <ref>Martz, E. Book review of ''Introduction to protein science—architecture, function, and genomics: Lesk, Arthur M. Biochem. Mol. Biol. Educ.'' 33:144-5 (2006). [http://link.springer.com/chapter/10.1007/978-1-4612-0401-5_21#page-1 DOI :10.1007/978-1-4612-0401-5_21#page-1]</ref>. 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 | + | 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 <ref>Martz, E. Book review of ''Introduction to protein science—architecture, function, and genomics: Lesk, Arthur M. Biochem. Mol. Biol. Educ.'' 33:144-5 (2006). [http://link.springer.com/chapter/10.1007/978-1-4612-0401-5_21#page-1 DOI :10.1007/978-1-4612-0401-5_21#page-1]</ref>. 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 cells(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.<ref>PMID:9817978</ref> |
==Structure== | ==Structure== | ||
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== The SCCA1 a tumor marker == | == The SCCA1 a tumor marker == | ||
| - | Cancer is | + | Cancer is characterized by the abnormal proliferation of a cellular clone that will form a tumor in a tissue. Tumor cells can migrate to the serum or urin and invade other tissues. Cancer is caused by damaged genes. Cancer can have several origins due to exogenous factors (tobacco, alcohol, UV) or endogenous factors (failure in DNA repair). |
| - | Tumor markers are | + | Tumor markers are compounds present in abnormal concentration in serum or urine in patients who develop a malignant tumor. Nevertheless tumor markers can appear in people who do not suffer from cancer or at low concentration in sick patients, this is called 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 sensitive. The dosage of several markers is necessary to establish the success or the failure of a treatment. |
| - | + | ||
| - | + | ||
| + | The SCCA is secreted by the tumor itself, it is a marker of mature cells. The SCCA is a glycoprotein present in the epithelium cells and released in the serum during epidermoid cervical cancer but also in epidermoid cancers suchh as lung, mouth, larynx, pharynx and esophagus. The cooncentration threshold is inferior at 1.5 µg for healthy patient.<ref>L. P. Kerbrat, Que faire des marqueurs tumoraux, Centre Eugène Marquis, Université de Rennes 1 [https://facmed.univ-rennes1.fr/wkf/stock/RENNES20110504094607cpiszkormarqueurs_tumoraux.coursDCEM1-02-2011.pdf DOI : stock/RENNES20110504094607cpiszkormarqueurs_tumoraux.coursDCEM1-02-2011.pdf]</ref> | ||
| + | [[Image:]] | ||
===SCCA role as a tumor marker=== | ===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 | + | SCCA is particularly used for the detecction of cancer of the uterine cervix. The correlation between SCCA concentration and lung tumor was proved. SCCA concentration increases in the presence of epidermoid lung tumor, independently of the differentiation state of the tumor<ref>PMID:1620906</ref>. SCCA is especially used to prognostic and follow the effects of the treatment in the lung cancer as second tumor marker <ref> Les marqueurs tumoraux Tableau d’aide à la description des principaux marqueurs tumoraux, Ketterhill laboratoires d’analyses médicales [http://www.llam.lu/fileadmin/media/newsletter/Marqueurs_Tum.pdf DOI : newsletter/Marqueurs_Tum.pdf] </ref> |
. High concentration of SCCA in the blood suggests the epithelial cells direct serpin activity to blood. This pathway is an active secretory process<ref>PMID:10956412</ref>. | . High concentration of SCCA in the blood suggests the epithelial cells direct serpin activity to blood. This pathway is an active secretory process<ref>PMID:10956412</ref>. | ||
===SCCA and cancer=== | ===SCCA and cancer=== | ||
| - | SCCA is not specific of one type of cancer. It can be associated to | + | SCCA is not specific of one type of cancer. It can be associated to mild broncho-pulmonarypathology, mild skin pathology. It does not depend on Tobacco consumption. SCCA is associated to cancer and non-malignant kidney pathology. It is quantified by immuno-analyzes, its half-life is 3 days. |
-In cervix cancer : | -In cervix cancer : | ||
| - | The SCCA | + | The SCCA increase is linked to the tumor weight and state of disease. Nevertheless 40 % of patients suffering from cervix cancer have a high SCCA blood concentration, it is not use for screening. An increase of the initial rate can be a sign of disease recurrence or persistence. It allows to follow the treatment efficiency such as chemotherapy, radiotherapy in patients. |
-In epidermoid bronchopulmonary cancer : | -In epidermoid bronchopulmonary cancer : | ||
| - | SCCA is not used for screening | + | SCCA is not used for screening. <ref>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]</ref> |
=Interaction= | =Interaction= | ||
===Hepatite B virus (HBV) interaction=== | ===Hepatite B virus (HBV) interaction=== | ||
| - | The SCCA may | + | The SCCA may play 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 SCCA 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 COS-7 (kidney cells of monkey transformed by antibody T of SV40). The binding complex of cells COS-7 with HBV seems to be more complex. The low density lipoprotein receptor-related protein (LRP) mediates the clearance of serpin-enzyme complex, the LRP may not enhance 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. <ref>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*[http://www.jbc.org/content/278/47/46709.full DOI 47/46709.full]</ref> |
===Receptor (LPR) interaction=== | ===Receptor (LPR) interaction=== | ||
| - | The serpin and serpin-protease complexes are able to | + | The serpin and serpin-protease complexes are able to bind the low density lipoprotein receptor-related protein (LPR). This binding allow to clear serpin- complexes from blood circulation. The ligand bind a clusters of rich cysteine residues. 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 <ref>PMID: PMC2709341</ref> |
= Disease = | = Disease = | ||
| - | Asthma is characterized by an obstruction of the interior respiratory tract and an excessive mucus secretion.<ref>Santé médecine, Hyperplasie définition[http://sante-medecine.commentcamarche.net/faq/13479-hyperplasie-definition DOI : faq/13479-hyperplasie-definition]</ref> 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 | + | Asthma is characterized by an obstruction of the interior respiratory tract and an excessive mucus secretion.<ref>Santé médecine, Hyperplasie définition[http://sante-medecine.commentcamarche.net/faq/13479-hyperplasie-definition DOI : faq/13479-hyperplasie-definition]</ref> 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 mist 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. <ref> PMID: 3058372 </ref> |
= Regulation = | = Regulation = | ||
| - | The E-cadherin can regulate the SCCA production in the squamous cell carcinoma of the uterin cervix. E- | + | The E-cadherin can regulate the SCCA production in the squamous cell carcinoma of the uterin cervix. E-cadherins are transmembrane proteins, they have a role in cell adhesion because they are able to form adherens junctions. They have to bind a Ca++ ion to work. Using an anti-E-cadherin antibody induces the dissociation of the cervical squamous cell carcinoma. It also induces a 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 mediates cell-cell adhesion and maintains SCCA production thanks to phosphatidyl inositol 3 kinase in squamous cell carcinoma.<ref> PMID: 14719077 </ref> |
= Structural highlights = | = Structural highlights = | ||
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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 cells(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 characterized by the abnormal proliferation of a cellular clone that will form a tumor in a tissue. Tumor cells can migrate to the serum or urin and invade other tissues. Cancer is caused by damaged genes. Cancer can have several origins due to exogenous factors (tobacco, alcohol, UV) or endogenous factors (failure in DNA repair). Tumor markers are compounds present in abnormal concentration in serum or urine in patients who develop a malignant tumor. Nevertheless tumor markers can appear in people who do not suffer from cancer or at low concentration in sick patients, this is called 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 sensitive. The dosage of several markers is necessary to establish the success or the failure of a treatment.
The SCCA is secreted by the tumor itself, it is a marker of mature cells. The SCCA is a glycoprotein present in the epithelium cells and released in the serum during epidermoid cervical cancer but also in epidermoid cancers suchh as lung, mouth, larynx, pharynx and esophagus. The cooncentration threshold is inferior at 1.5 µg for healthy patient.[5] [[Image:]]
SCCA role as a tumor marker
SCCA is particularly used for the detecction of cancer of the uterine cervix. The correlation between SCCA concentration and lung tumor was proved. SCCA concentration increases in 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 broncho-pulmonarypathology, mild skin pathology. It does not depend on Tobacco consumption. SCCA is associated to cancer and non-malignant kidney pathology. It is quantified by immuno-analyzes, its half-life is 3 days.
-In cervix cancer : The SCCA increase is linked to the tumor weight and state of disease. Nevertheless 40 % of patients suffering from cervix cancer have a high SCCA blood concentration, it is not use for screening. An increase of the initial rate can be a sign of disease recurrence or persistence. It allows to follow the treatment efficiency such as chemotherapy, radiotherapy in patients.
-In epidermoid bronchopulmonary cancer : SCCA is not used for screening. [9]
Interaction
Hepatite B virus (HBV) interaction
The SCCA may play 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 SCCA 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 COS-7 (kidney cells of monkey transformed by antibody T of SV40). The binding complex of cells COS-7 with HBV seems to be more complex. The low density lipoprotein receptor-related protein (LRP) mediates the clearance of serpin-enzyme complex, the LRP may not enhance 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 bind the low density lipoprotein receptor-related protein (LPR). This binding allow to clear serpin- complexes from blood circulation. The ligand bind a clusters of rich cysteine residues. 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 mist 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-cadherins are transmembrane proteins, they have a role in cell adhesion because they are able to form adherens junctions. They have to bind a Ca++ ion to work. Using an anti-E-cadherin antibody induces the dissociation of the cervical squamous cell carcinoma. It also induces a 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 mediates cell-cell adhesion and maintains SCCA production thanks to phosphatidyl inositol 3 kinase in squamous cell carcinoma.[14]
Structural highlights
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</StructureSection>
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Suminami Y, Nawata S, Kato H. Biological role of SCC antigen. Tumour Biol. 1998;19(6):488-93. PMID:9817978
- ↑ L. P. Kerbrat, Que faire des marqueurs tumoraux, Centre Eugène Marquis, Université de Rennes 1 DOI : stock/RENNES20110504094607cpiszkormarqueurs_tumoraux.coursDCEM1-02-2011.pdf
- ↑ 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
- ↑ Les marqueurs tumoraux Tableau d’aide à la description des principaux marqueurs tumoraux, Ketterhill laboratoires d’analyses médicales DOI : newsletter/Marqueurs_Tum.pdf
- ↑ 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
- ↑ 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]
- ↑ 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
- ↑ PMID: PMC2709341
- ↑ Santé médecine, Hyperplasie définitionDOI : faq/13479-hyperplasie-definition
- ↑ 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
- ↑ 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
