Squamous cell carcinoma antigen 1

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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. 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.

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 from the blood or lymph 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 blood 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. This molecule possesses monoclonal antibodies obtain by the injection of homogenate tumor in mice. 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.

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 [1]. SCCA is especially used to prognostic and follow the effects of the treatment in the lung cancer as second tumor marker [2]. High concentration of SCCA in the blood suggests the epithelial cells direct serpin activity to blood. This pathway is an active secretory process.

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

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.

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. .

Disease

Asthma is characterized by an obstruction of the interior respiratory tract and an excessive mucus secretion. 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.

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.

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