Characterization of the state of differentiation of six newly established human non-small-cell lung cancer cell lines

Our plain-English summary of Characterization of the state of differentiation of six newly established human non-small-cell lung cancer cell lines, by G. Bepler, A. Koehler, P. Kiefer, et al (Differentiation; Research in Biological Diversity, 1988).

The study

• Authors: G. Bepler, A. Koehler, P. Kiefer, K. Havemann, K. Beisenherz, G. Jaques, C. Gropp, M. Haeder
• Journal: Differentiation; Research in Biological Diversity
• Published: 1988;37(2):158-71
• Cited by: 111 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Six new non-small-cell lung cancer (NSCLC) cell lines were established directly from human tissue or indirectly via nude mouse xenografts in serum-supplemented media with success rates of 8% and 13%, respectively. They comprised one adenocarcinoma (ADLC-5M2), two squamous cell carcinomas (EPLC-32M1, EPLC-65H), two large cell carcinomas (LCLC-97TM1, LCLC-103H), and one malignant biphasic mesothelioma (MSTO-211H). All cell lines grew adherent to culture vessels with population doubling times (PDT) of 16-40 h, formed colonies in soft agarose with efficiencies of 0.1%-5.1%, and all grew in athymic nude mice. Xenograft histologies appeared as follows: (a) undifferentiated carcinomas with feeble resemblance to the original tumors in the case of adenocarcinomas and squamous cell carcinomas; (b) large cell carcinoma with high resemblance to the original tumor; (c) an undifferentiated tumor with predominance of large epithelial cells and few fibrous cells in the case of mesothelioma. Human chorionic gonadotropin (HCG) was found by radioimmunoassay and high-affinity binding sites for epidermal growth factor (EGF) by radio-receptor assay in 4/4 cell lines. A very low activity of L-DOPA decarboxylase (DDC) was detectable only in the adenocarcinoma cell line. All cell lines overexpressed the c-myc protooncogene, and no gene rearrangement or amplification was observed. Chromosome analysis revealed modal chromosome numbers of 70-73 in ADLC-5M2, EPLC-32M1, EPLC-65H, and MSTO-211H. Cell lines derived from large cell carcinoma had modal values of 65 and 170 and a wider chromosome distribution than all other cell lines. A NSCLC specific chromosomal aberration has been undetectable until now. These cell lines may aid in elucidating the biology of NSCLC and its interrelationship to other lung tumors.

In plain English

This laboratory study from Marburg and Giessen, Germany, described six new cell lines grown from human tumors that the authors classed as non-small-cell lung cancer. The authors counted malignant mesothelioma within this group. From July 1981 through December 1985 they received 53 tumor specimens from patients in Marburg. Growing cells directly from the specimens produced four lines, an 8% rate. Growing tumors first in nude mice produced two more, for an overall indirect rate of 13%. One line, MSTO-211H, came from the pleural effusion of a 62-year-old man with malignant biphasic mesothelioma who had had no prior therapy. In culture it showed two cell types. In mice it formed an undifferentiated tumor made mostly of large cells, with some fibrous elongated cells. Like all six lines, it overexpressed the c-myc gene, and no amplification was found. Its modal chromosome number fell in the 70-73 range shared by four lines. No chromosome change common to all lines was found. The authors concluded that they could permanently grow lines of the major types, including malignant mesothelioma. The article does not report asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study establishing and characterizing human tumor cell lines (cell culture and nude mouse xenografts)
• Who was studied: 53 tumor specimens from patients with non-small-cell lung cancer at the Philipps University Medical Center, Marburg, Federal Republic of Germany, July 1981 through December 1985. They included 3 malignant mesotheliomas (1 primary tumor, 2 pleural effusions). The mesothelioma cell line MSTO-211H came from the pleural effusion of a 62-year-old Caucasian man with no prior therapy.
• Exposure: No asbestos or other environmental or occupational exposure is reported. The study characterized cell lines derived from tumors.
• Main results:
  • Direct culture of the specimens established four primary cell lines (EPLC-32H, EPLC-65H, LCLC-103H, MSTO-211H), an establishment rate of 8%.
  • The indirect approach via nude mouse xenografts gave two more cell lines (ADLC-5M2, LCLC-97TM1), an overall indirect establishment rate of 13%.
  • For malignant mesothelial cells, the best approach was 2 weeks in RTSI medium, then 4 weeks in RTS12.5 medium, then R10 medium.
  • The xenograft of the mesothelioma line MSTO-211H was an undifferentiated tumor made mostly of large cells, with some fibrous elongated cells.
  • Population doubling times were 16-20 h for the adenocarcinoma, squamous cell carcinoma and malignant mesothelioma lines. The large cell carcinoma lines had 26 h and 40 h.
  • All lines formed colonies in soft agarose with efficiencies of 1.6% to 5.1%, except LCLC-103H at 0.1%.
  • High-affinity EGF binding sites were found on all four cell lines tested, with maximum binding of 490 to 1000 fmol/mg protein.
  • c-myc was the only one of the four genes tested (c-myc, N-myc, L-myc, c-myb) that was overexpressed in the cell lines. The authors described all six lines as having elevated c-myc mRNA levels, and no c-myc amplification was detected.
  • Modal chromosome numbers were 70-73 in the ADLC-5, EPLC-32, EPLC-65 and MSTO-211 lines. They were 65 in LCLC-97TM1 and 170 in LCLC-103H. No chromosomal aberration common to all lines was found.
  • Double-minute chromosomes were found only in the mesothelioma lines: in 1 of 50 metaphases of MSTO-211H and 2 of 50 metaphases of MSTO-211M1.
• The authors' conclusion: The authors concluded that they could permanently grow non-small-cell lung cancer cell lines of the major histological types, including malignant mesothelioma, and that these lines may help clarify the biology of this cancer group.
• Limitations the authors state:
  • The authors stated that establishment rates were low and must be raised to obtain a large representative panel of cell lines, particularly for squamous cell carcinoma.
  • The authors judged that the small gain from the nude mouse approach did not justify its effort and cost.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Adenocarcinoma, Squamous Cell Carcinoma, Carcinoma, Biphasic Mesothelioma, Mesothelioma.

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