Development of specific monoclonal antibodies and a sensitive discriminatory immunoassay for the circulating tumor markers SCCA1 and SCCA2

Sule Çataltepe, Charles Schick, Cliff J. Luke, Stephen C O Pak, Daniel Goldfarb, Philip Chen, Milenko J. Tanasiyevic, Marshall R. Posner, Gary A. Silverman

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The squamous cell carcinoma antigen (SCCA) serves as a serologic marker for advanced squamous cell carcinomas (SCC) of the uterine cervix, lung, esophagus, head and neck and vulva. Elevations in serum levels of SCCA following treatment for SCC correlate with tumor relapse or metastasis. Recent molecular studies show that SCCA is transcribed by two nearly identical genes (SCCA1 and SCCA2) that encode for members of the high molecular weight serine proteinase inhibitor (serpin) family. Despite a high degree of similarity in their amino acid sequences, SCCA1 and SCCA2 have distinct biochemical properties: SCCA1 is an inhibitor of papain like cysteine proteinases, such as cathepsins (cat) L, S and K, whereas SCCA2 inhibits chymotrypsin-like serine proteinases, catG and mast cell chymase. In this paper, we report the generation and characterization of anti-SCCA1 and anti-SCCA2 specific monoclonal antibodies (MAbs). Using these MAbs, we developed an enzyme-linked immunoassay (ELISA) that discriminated between SCCA1 and SCCA2 without any cross-reaction. This assay measured both the native and complexed forms of SCCA1 and SCCA2. The sensitivity of detection of SCCA1 and SCCA2 assays were 0.17 ngml-1 and 0.19 ngml-1, respectively. Mean inter- and intra-assay coefficients of variation were 12.1% and 9.9% for SCCA1 assay and 12% and 8.8% for SCCA2 assay, respectively. Recovery and parallellism studies indicated that SCCA1 and SCCA2 were detected in the plasma and amniotic fluids without any major interference by the biologic fluid components. This assay provides a simple and accurate procedure for the quantitation of total SCCA1 and SCCA2. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)107-127
Number of pages21
JournalClinica Chimica Acta
Volume295
Issue number1-2
DOIs
StatePublished - May 1 2000

Fingerprint

Tumor Biomarkers
Immunoassay
Assays
cathepsin S
Monoclonal Antibodies
Squamous Cell Carcinoma
Cathepsin K
Chymases
Cathepsin L
Serine Proteinase Inhibitors
Vulva
Papain
Cysteine Proteases
Cross Reactions
Chymotrypsin
Serine Proteases
Amniotic Fluid
Immunoenzyme Techniques
Mast Cells
Cervix Uteri

Keywords

  • ELISA
  • Monoclonal antibody
  • SCCA1
  • SCCA2
  • Serpin
  • Squamous cell carcinoma
  • Squamous cell carcinoma antigen

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Development of specific monoclonal antibodies and a sensitive discriminatory immunoassay for the circulating tumor markers SCCA1 and SCCA2. / Çataltepe, Sule; Schick, Charles; Luke, Cliff J.; Pak, Stephen C O; Goldfarb, Daniel; Chen, Philip; Tanasiyevic, Milenko J.; Posner, Marshall R.; Silverman, Gary A.

In: Clinica Chimica Acta, Vol. 295, No. 1-2, 01.05.2000, p. 107-127.

Research output: Contribution to journalArticle

Çataltepe, S, Schick, C, Luke, CJ, Pak, SCO, Goldfarb, D, Chen, P, Tanasiyevic, MJ, Posner, MR & Silverman, GA 2000, 'Development of specific monoclonal antibodies and a sensitive discriminatory immunoassay for the circulating tumor markers SCCA1 and SCCA2', Clinica Chimica Acta, vol. 295, no. 1-2, pp. 107-127. https://doi.org/10.1016/S0009-8981(00)00197-2
Çataltepe, Sule ; Schick, Charles ; Luke, Cliff J. ; Pak, Stephen C O ; Goldfarb, Daniel ; Chen, Philip ; Tanasiyevic, Milenko J. ; Posner, Marshall R. ; Silverman, Gary A. / Development of specific monoclonal antibodies and a sensitive discriminatory immunoassay for the circulating tumor markers SCCA1 and SCCA2. In: Clinica Chimica Acta. 2000 ; Vol. 295, No. 1-2. pp. 107-127.
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AU - Goldfarb, Daniel

AU - Chen, Philip

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N2 - The squamous cell carcinoma antigen (SCCA) serves as a serologic marker for advanced squamous cell carcinomas (SCC) of the uterine cervix, lung, esophagus, head and neck and vulva. Elevations in serum levels of SCCA following treatment for SCC correlate with tumor relapse or metastasis. Recent molecular studies show that SCCA is transcribed by two nearly identical genes (SCCA1 and SCCA2) that encode for members of the high molecular weight serine proteinase inhibitor (serpin) family. Despite a high degree of similarity in their amino acid sequences, SCCA1 and SCCA2 have distinct biochemical properties: SCCA1 is an inhibitor of papain like cysteine proteinases, such as cathepsins (cat) L, S and K, whereas SCCA2 inhibits chymotrypsin-like serine proteinases, catG and mast cell chymase. In this paper, we report the generation and characterization of anti-SCCA1 and anti-SCCA2 specific monoclonal antibodies (MAbs). Using these MAbs, we developed an enzyme-linked immunoassay (ELISA) that discriminated between SCCA1 and SCCA2 without any cross-reaction. This assay measured both the native and complexed forms of SCCA1 and SCCA2. The sensitivity of detection of SCCA1 and SCCA2 assays were 0.17 ngml-1 and 0.19 ngml-1, respectively. Mean inter- and intra-assay coefficients of variation were 12.1% and 9.9% for SCCA1 assay and 12% and 8.8% for SCCA2 assay, respectively. Recovery and parallellism studies indicated that SCCA1 and SCCA2 were detected in the plasma and amniotic fluids without any major interference by the biologic fluid components. This assay provides a simple and accurate procedure for the quantitation of total SCCA1 and SCCA2. Copyright (C) 2000 Elsevier Science B.V.

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