Expression of epidermal growth factor receptors in human lung tumors

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80 3. BASIC BIOLOGY Expression of Epidermal Growth Factor Receptors in Human Lung Tumors. Hwang, D.L., Tay, Y.-C., Lin, S.S., Lev- Ran, A. Department of Endocrinology, City of Hope Medical Center, Duarte, CA 91010, U.S.A. Cancer 58: 2260-2263, 1986. Using the adjacent histologically normal tissues obtained from the same patients as controls, 6 human lung tumors were studied for the activities of epidermal growth factor (EGF) receptor binding, and receptor autophosphorylation. There was a 1.2- to 2.8-fold increase in EGF receptor ac- tivities in lung tumors due to an in- crease in the number of receptors without changes in their affinity. The increase had no direct correlation with the degree of differentiation or the type of lung tumors. The elevated expression of EGF receptor may be one of the characteris- tics in lung tumors. Epidermal growth factor and its receptor also may play a role in the regulatory mechanisms during tumorigenesis. Interferon Gamma and Granulocyte/Macrophage Colony-Stimulating Factor Inhibit Growth and Induce Antigens Characteristic of Myeloid Differentiation in Small-Cell Lung Cancer Cell Lines. Ruff, M.R., Farrar, W.L., Pert, C.B. Cel- lular Immunology Section, Laboratory of Microbiology and Immunology, National In- stitute of Dental Research, National In- stitutes of Health, Bethesda, MD 20892, U.S.A. Proc. Natl. Acad. Sci. U.S.A. 83: 6613-6617, 1986. The expression of several macrophage and hemopoietic cell surface markers recently described on small-cell lung cancer (SCLC) cell lines was studied by use of flow cytometry. The antigens Leu- M3, Leu-7, and HLA-DR were examined for their modulation by human interferon gamma and granulocyte/macrophage colony- stimulating factor (GM-CSF). Both of these lymphokines generally induced en- hanced expression of hemopoietic markers in several SCLC lines. A differential response to these two hormones was observed, in that qualitative and quanta- tive differences in marker modulation amon the tested cell lines were apparent. In addition to regulating the antigenic phenotype of these cells, both interferon gamma and GM-CSF had antiproliferative effects on SCLC lines as determined by (3H) thymidine incorporation and clonal growth in agar. These results suggest that interferon gamma and GM-CSF promote a differentiation process in SCLC cell lines that has characteristics in common with myeloid differentiation. These find- ings support the theory that SCLC tumors are hemopoietic cells tha~ arise from macrophages or their precursors and sug- gest new therapeutic modalities for the treatment of lung cancer. Distribution of a Squamous Cell Lung Carcinoma-Associated Antigen, KA-32 in Human Tissues and Sera Defined by Monoclonal Antibodt KM-32. Hanai, N., Shitara, K., Yoshida, H. Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo'194, Japan. Cancer Res. 46: 5206-5210, 1986. The distribution of a variant of blood group A antigen recognized by a murine monoclonal antibody, KM-32, gen- erated against human squamous cell lung carcinoma was investigated in various tissues and sera. By immunoperoxidase staining, the antibody was found to react with a number of lung carcinoma tissues of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, and several other tumor tissues. Positive staining was also observed in a small number of cells of some normal tissues, such as bronchiolar epithelium, gastroin- testinal glands, and convoluted tubules of the kidney. The antibody could also be used in detecting macromolecular antigens, designated KA-32, in sera of patients with lung cancer. The antigen level in serum was determined by an in- hibition assay using purified KM-32. The higher level of inhibition was seen in sera from over half of patients with lung cancer and patients with benign diseases when compared with those in sera from healthy adults. Purification of the an- tigen in serum was performed by gel filtration chromatography, immunoaffinity chromatography, and polycrylamide gradient gel electrophoresis. Purified antigen exhibited a glycoprotein nature, and its molecular weight was estimated at more than 500,000. Two Novel Cell Surface Antigens on Small Cell Lung Carcinoma Defined by Mouse Monoclonal Antibodies NE-25 and PE-35. Takahishi, T., Ueda, R., Song, X, et al. Department of Thoracic Surgery, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Japan. Cancer Res. 46: 4770- 4775, 1986. Two mouse monoclonal antibodies, NE- 25 and PE-35, defining novel cell surface antigens of small cell lung carcinoma (SCLC) were produced. The molecular weight of NE-25 and PE-35 antigens es- timated by radioimmunoprecipitation was 25,000 and 35,000, respectively. NE-25 antigen was expressed on the majority of cell lines and tumor specimens of SCLC among lung carcinoma. These NE-25 posi- tive cell lines showed typical growth morphology as SCLC classic lines and expressed high levels of neuroendocrine biomarkers, such as aromatic L-amino acid decarboxylase, while NE-25 antigen- negative lines lacked apparent neuroen- docrine properties. This antigen was expressed also on a subset of neoplastic cells with (neuro)endocrine properties, including pulmonary carcinoid, and on various tumors of nervous tissues, such

Transcript of Expression of epidermal growth factor receptors in human lung tumors

Page 1: Expression of epidermal growth factor receptors in human lung tumors

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3. BASIC BIOLOGY

Expression of Epidermal Growth Factor Receptors in Human Lung Tumors. Hwang, D.L., Tay, Y.-C., Lin, S.S., Lev- Ran, A. Department of Endocrinology, City of Hope Medical Center, Duarte, CA 91010, U.S.A. Cancer 58: 2260-2263, 1986.

Using the adjacent histologically normal tissues obtained from the same patients as controls, 6 human lung tumors were studied for the activities of epidermal growth factor (EGF) receptor binding, and receptor autophosphorylation. There was a 1.2- to 2.8-fold increase in EGF receptor ac- tivities in lung tumors due to an in- crease in the number of receptors without changes in their affinity. The increase had no direct correlation with the degree of differentiation or the type of lung tumors. The elevated expression of EGF receptor may be one of the characteris- tics in lung tumors. Epidermal growth factor and its receptor also may play a role in the regulatory mechanisms during tumorigenesis.

Interferon Gamma and Granulocyte/Macrophage Colony-Stimulating Factor Inhibit Growth and Induce Antigens Characteristic of Myeloid Differentiation in Small-Cell Lung Cancer Cell Lines. Ruff, M.R., Farrar, W.L., Pert, C.B. Cel- lular Immunology Section, Laboratory of Microbiology and Immunology, National In- stitute of Dental Research, National In- stitutes of Health, Bethesda, MD 20892, U.S.A. Proc. Natl. Acad. Sci. U.S.A. 83: 6613-6617, 1986.

The expression of several macrophage and hemopoietic cell surface markers recently described on small-cell lung cancer (SCLC) cell lines was studied by use of flow cytometry. The antigens Leu- M3, Leu-7, and HLA-DR were examined for their modulation by human interferon gamma and granulocyte/macrophage colony- stimulating factor (GM-CSF). Both of these lymphokines generally induced en- hanced expression of hemopoietic markers in several SCLC lines. A differential response to these two hormones was observed, in that qualitative and quanta- tive differences in marker modulation amon the tested cell lines were apparent. In addition to regulating the antigenic phenotype of these cells, both interferon gamma and GM-CSF had antiproliferative effects on SCLC lines as determined by (3H) thymidine incorporation and clonal growth in agar. These results suggest that interferon gamma and GM-CSF promote a differentiation process in SCLC cell lines that has characteristics in common with myeloid differentiation. These find- ings support the theory that SCLC tumors are hemopoietic cells tha~ arise from macrophages or their precursors and sug- gest new therapeutic modalities for the treatment of lung cancer.

Distribution of a Squamous Cell Lung Carcinoma-Associated Antigen, KA-32 in Human Tissues and Sera Defined by Monoclonal Antibodt KM-32. Hanai, N., Shitara, K., Yoshida, H. Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo'194, Japan. Cancer Res. 46: 5206-5210, 1986.

The distribution of a variant of blood group A antigen recognized by a murine monoclonal antibody, KM-32, gen- erated against human squamous cell lung carcinoma was investigated in various tissues and sera. By immunoperoxidase staining, the antibody was found to react with a number of lung carcinoma tissues of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, and several other tumor tissues. Positive staining was also observed in a small number of cells of some normal tissues, such as bronchiolar epithelium, gastroin- testinal glands, and convoluted tubules of the kidney. The antibody could also be used in detecting macromolecular antigens, designated KA-32, in sera of patients with lung cancer. The antigen level in serum was determined by an in- hibition assay using purified KM-32. The higher level of inhibition was seen in sera from over half of patients with lung cancer and patients with benign diseases when compared with those in sera from healthy adults. Purification of the an- tigen in serum was performed by gel filtration chromatography, immunoaffinity chromatography, and polycrylamide gradient gel electrophoresis. Purified antigen exhibited a glycoprotein nature, and its molecular weight was estimated at more than 500,000.

Two Novel Cell Surface Antigens on Small Cell Lung Carcinoma Defined by Mouse Monoclonal Antibodies NE-25 and PE-35. Takahishi, T., Ueda, R., Song, X, et al. Department of Thoracic Surgery, Nagoya University School of Medicine, Showa-ku, Nagoya 466, Japan. Cancer Res. 46: 4770- 4775, 1986.

Two mouse monoclonal antibodies, NE- 25 and PE-35, defining novel cell surface antigens of small cell lung carcinoma (SCLC) were produced. The molecular weight of NE-25 and PE-35 antigens es- timated by radioimmunoprecipitation was 25,000 and 35,000, respectively. NE-25 antigen was expressed on the majority of cell lines and tumor specimens of SCLC among lung carcinoma. These NE-25 posi- tive cell lines showed typical growth morphology as SCLC classic lines and expressed high levels of neuroendocrine biomarkers, such as aromatic L-amino acid decarboxylase, while NE-25 antigen- negative lines lacked apparent neuroen- docrine properties. This antigen was expressed also on a subset of neoplastic cells with (neuro)endocrine properties, including pulmonary carcinoid, and on various tumors of nervous tissues, such