Growth of human tumor xenografts in SCID mice quantified using an immunoassay for tumor marker protein in serum

• Published in: Journal of immunological methods Vol. 233; no. 1; pp. 57 - 65
• Main Authors: Conway, Thomas F, Sabel, Michael S, Sugano, Masahiko, Frelinger, John G, Egilmez, Nejat K, Chen, Fang-An, Bankert, Richard B
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13-01-2000; Elsevier
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Biomarkers, Tumor - blood; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - surgery; Enzyme-Linked Immunosorbent Assay - methods; Experimental tumors, general aspects; Genetic Vectors; Humans; Lung Neoplasms - blood; Lung Neoplasms - genetics; Lung Neoplasms - surgery; Male; Medical sciences; Mice; Mice, SCID; Neoplasm Transplantation; Neoplasms, Experimental - blood; Neoplasms, Experimental - genetics; Neoplasms, Experimental - surgery; prostate-specific antigen; Prostate-Specific Antigen - blood; Prostate-Specific Antigen - genetics; PSA; Rabbits; SCID mice; Serum marker; Transfection; Transplantation, Heterologous; Tumor Cells, Cultured; Tumors; Xenograft; Serum marker; SCID, severe combined immunodeficient mice; Xenograft; Transfection; PSA, prostate specific antigen; TIL, tumor infiltrating leukocyte; TMB, 3,3′,5,5′-tetra methyl-benzidine; SCID mice; HuPBL, human peripheral blood leukocyte; PSA; Human; Rodentia; Biological marker; Heterograft; Immunological method; Prostate specific antigen; Vertebrata; Mammalia; Investigation method; Mouse; Serum; Tumor; Severe; Combined immune deficiency
• ISSN: 0022-1759; 1872-7905
• DOI: 10.1016/S0022-1759(99)00190-8

The accurate measurement of the response of a tumor to a given treatment is critical to evaluating novel therapeutic modalities. An experimental design is reported here that can be generally applied to monitoring human tumor xenografts growing in immunodeficient mice. A human non-small cell lung tumor cell line was transfected with a mammalian expression vector containing the gene encoding human prostate specific antigen (PSA) and has been shown to grow progressively following the subcutaneous, intraperitoneal and intravenous inoculation of the tumor into severe combined immunodeficient (SCID) mice. The transfected human tumor cells produce PSA that accumulates in the sera of all tumor inoculated SCID mice. An enzyme-linked immunoassay using a rabbit polyclonal and a mouse monoclonal antibody specific for PSA was designed and tested for the detection and quantification of serum PSA in tumor-bearing mice. Over a 5-week period, the serum levels of PSA of mice inoculated subcutaneously with the tumor increased progressively, and the estimated tumor volumes correlated with the amount of PSA detected in the serum. Serum PSA levels correlated even better with total tumor mass following the intraperitoneal inoculation of tumor cells into SCID mice. Serum PSA levels fell rapidly following the surgical debulking of tumor xenograft, reaching background levels of PSA in the serum 1 week after tumor removal. Serum PSA levels were also observed in SCID mice inoculated intravenously with a PSA transfected human lung tumor cell line adapted to grow orthotopically in the lung. The transfection of human tumors with a tumor marker and the use of an immunoassay to detect this marker establish an experimental design that provides a reliable, non-invasive, accurate and simple approach to monitor and quantify the growth of human tumor xenografts in SCID mice.