Abstract
Fifteen tumor-containing specimens were obtained directly from patients with small cell carcinoma of the lung and tested for their ability to grow in serum-supplemented medium and in serum-free medium supplemented with hydrocortisone, insulin, transferrin, estrogen, and selenium (HITES). The tumor cells replicated in 14 of 15 cases (93%) in the HITES medium and in 10 of 15 cases (67%) in the serum-supplemented medium. The neoplastic origin of the cells growing in the HITES medium was confirmed by standard cytologic criteria, by DNA content analysis using flow cytometry, and by their ability to form colonies in agarose and tumors in athymic nude mice. While the tumor cells had very similar morphologies in both media, the serum-free medium did not support the growth of nonmalignant stromal cells, and essentially pure cultures of replicating tumor cells were obtained 7-10 days after plating. The selectivity of the HITES medium was demonstrated by the failure of cells to grow in 20 specimens cytologically negative for small cell carcinoma and in 9 of 10 specimens containing other tumor types (including other types of lung cancer). The results demonstrate that a chemically defined medium, determined by work on tissue culture-adapted human tumor lines, can support the selective growth of tumor specimens obtained directly from patients. Such selective formulas are probably specific for different tumor types and thus could be used for diagnosis, drug sensitivity testing in vitro, and identification of factors regulating tumor growth. All of these have direct application to patient treatment.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bottenstein J. E., Sato G. H. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979 Jan;76(1):514–517. doi: 10.1073/pnas.76.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bottenstein J. E., Skaper S. D., Varon S. S., Sato G. H. Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. Exp Cell Res. 1980 Jan;125(1):183–190. doi: 10.1016/0014-4827(80)90202-5. [DOI] [PubMed] [Google Scholar]
- Bottenstein J., Hayashi I., Hutchings S., Masui H., Mather J., McClure D. B., Ohasa S., Rizzino A., Sato G., Serrero G. The growth of cells in serum-free hormone-supplemented media. Methods Enzymol. 1979;58:94–109. doi: 10.1016/s0076-6879(79)58127-0. [DOI] [PubMed] [Google Scholar]
- Bunn P. A., Jr, Whang-Peng J., Carney D. N., Schlam M. L., Knutsen T., Gazdar A. F. DNA content analysis by flow cytometry and cytogenetic analysis in mycosis fungoides and Sézary syndrome. J Clin Invest. 1980 Jun;65(6):1440–1448. doi: 10.1172/JCI109808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carney D. N., Gazdar A. F., Minna J. D. Positive correlation between histological tumor involvement and generation of tumor cell colonies in agarose in specimens taken directly from patients with small-cell carcinoma of the lung. Cancer Res. 1980 Jun;40(6):1820–1823. [PubMed] [Google Scholar]
- Gazdar A. F., Carney D. N., Russell E. K., Sims H. L., Baylin S. B., Bunn P. A., Jr, Guccion J. G., Minna J. D. Establishment of continuous, clonable cultures of small-cell carcinoma of lung which have amine precursor uptake and decarboxylation cell properties. Cancer Res. 1980 Oct;40(10):3502–3507. [PubMed] [Google Scholar]
- Hayashi I., Sato G. H. Replacement of serum by hormones permits growth of cells in a defined medium. Nature. 1976 Jan 15;259(5539):132–134. doi: 10.1038/259132a0. [DOI] [PubMed] [Google Scholar]
- Ihde D. C., Simms E. B., Matthews M. J., Cohen M. H., Bunn P. A., Minna J. D. Bone marrow metastases in small cell carcinoma of the lung: frequency, description, and influence on chemotherapeutic toxicity and prognosis. Blood. 1979 Apr;53(4):677–686. [PubMed] [Google Scholar]
- Krishan A. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol. 1975 Jul;66(1):188–193. doi: 10.1083/jcb.66.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mather J. P., Sato G. H. The growth of mouse melanoma cells in hormone-supplemented, serum-free medium. Exp Cell Res. 1979 Apr;120(1):191–200. doi: 10.1016/0014-4827(79)90549-4. [DOI] [PubMed] [Google Scholar]
- Murakami H., Masui H. Hormonal control of human colon carcinoma cell growth in serum-free medium. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3464–3468. doi: 10.1073/pnas.77.6.3464. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pettengill O. S., Sorenson G. D., Wurster-Hill D. H., Curphey T. J., Noll W. W., Cate C. C., Maurer L. H. Isolation and growth characteristics of continuous cell lines from small-cell carcinoma of the lung. Cancer. 1980 Mar 1;45(5):906–918. doi: 10.1002/1097-0142(19800301)45:5<906::aid-cncr2820450513>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
- Rees L. H. The biosynthesis of hormones by non-endocrine tumours--a review. J Endocrinol. 1975 Oct;67(1):143–175. doi: 10.1677/joe.0.0670143. [DOI] [PubMed] [Google Scholar]
- Rizzino A., Sato G. Growth of embryonal carcinoma cells in serum-free medium. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1844–1848. doi: 10.1073/pnas.75.4.1844. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salmon S. E., Hamburger A. W., Soehnlen B., Durie B. G., Alberts D. S., Moon T. E. Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N Engl J Med. 1978 Jun 15;298(24):1321–1327. doi: 10.1056/NEJM197806152982401. [DOI] [PubMed] [Google Scholar]
- Simms E., Gazdar A. F., Abrams P. G., Minna J. D. Growth of human small cell (oat cell) carcinoma of the lung in serum-free growth factor-supplemented medium. Cancer Res. 1980 Dec;40(12):4356–4363. [PubMed] [Google Scholar]
- Taub M., Chuman L., Saier M. H., Jr, Sato G. Growth of Madin-Darby canine kidney epithelial cell (MDCK) line in hormone-supplemented, serum-free medium. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3338–3342. doi: 10.1073/pnas.76.7.3338. [DOI] [PMC free article] [PubMed] [Google Scholar]