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We have investigated a panel of human lung cancer cell lines representing the major groups of lung cancer, i.e. small-cell carcinoma (KC) and the group of non-KC, consisting of squamous-cell carci- noma (SQC), adenocarcinoma (ADC) and large-cell carcinoma (LCC), for their expression of certain growth factor genes. Messenger RNA from each cell line was hybridized with probes for platelet-derived growth factor (PDGF) A- and B-chains, insulin-like growth factor (lGF)-1 and -11, transforming growth factor (TGF)-_ and -6, epidermal growth factor (EGF) as well as a probe for the EGF-receptor. All non- SCC cell lines examined showed expression of the PDGF A-chain gene. ThePDGFB-chainandTGF-Bgenes wereexpressedinallnon-SCCcell lines but one, H-125 (ADC). TGF-_ gene expression was demonstrated in the SQC cell line U-1752, in both ADC cell lines (H-23 and H-125) and in one of the 3 LCC ccl1 lines, U-l 810. IGF-II was only transcribed in the LCC cell line U-l 8 IO. The EGF-receptor was detected in all non- SCCcell lines but one, H-661 (LCC). Neither IGF-I n0rEGFtranscript.s could be seen in any of the IO cell lines examined. In contrast to the non- SCC cell lines, the 4 KC lines were constantly negative for the probes employed in this study. The frequent and heterogeneous expression of growth factor transcripts in all non-SCC studied, but not SCC-cell lines, may contribule to the difference in biological behaviour observed in vivo and in vitro between the 2 major lung cancer entities.
A carbohydrate epitope associated with human squamous lung cancer. Martensson S, Due C, Pahlsson P et al. Department of Clinical Che- misery, University Hospital, S-221 85 Lund. Cancer Res 1988;48:2125- 31.
A moncclonal antibody, 43-9F, specifically recognizes a tumor- associated antigen expressed both on surface membrane glycoproteins and on secreted soluble mucins of human squamous lung carcinoma (SLC) cells, and the corresponding antigen can be detected as a circulating tumor marker in plasma of SLC patients. Thin-layer chroma- tography immunostaining of neutral glycolipids extracted from SLC cells reveals a 43-9F-reactive glycolipid whose carbohydrate structure, as determined by fast atom bombardment-mass spectrometry, is iden- tical with that of an Le(a)-active pentaglycosylceramide described previously: Gall3l-3[Fuc_l-4]-GlcNAcBl-3Gall3l-4Glc-Cer. How- ever, the Le(a)-active oligosaccharide hapten, lacto-N-fucopentaose 11, with the same carbohydrate strucLure, fails to inhibit binding of43-9F, and a well-characterized anti-Le(a) monoclonal antibody blocks only 40% of 43-9F binding sites on SLC cells, suggesting that the major epitopc recognized by43-9F ismorecomplex than tbeLe(a)epilope. To search for a higher affinity 43-9F epitope among more complex oligo- saccharides, a mixture of tritiated neutral oligosaccharide alditols from pooled human milk was passed through a 43-9F affinity column. A major retarded oligosaccharide was purified by high-performance liq- uid chromatography and shown by fast atom bombardment-mass spec- trometry to have the following structure: GalSI-3[Fuc_I -4]GlcNAcBl- 3Gall3-4(Fuc_l-3]GlcNAcBl-3Gallll-4Glc Oligosaccharides con- taining this sugar sequence arc at least IOO-fold more active than lacto- N-fucopcnlaose II as competitive inhibitors of 43-9F. Thus, antibody 43.9F binds to the above difucosyl Le(a)-X determinant with high affinity and weakly cross-reacts with the Le(a) antigen under some conditions such as occurs in thin-layer chromatography and enzyme- linked immunosorbent assay where multiple weak interactions of the decavalent IgM antibody may occur.
studiedinanewcaninemodelthatissimplerandmorecosteffectvethan previously reported methods of orthotopic endobronchial carcinogene- sis. Short segments of bronchus, obtained by pneumonectomy, were placed on the back of IO dogs in the form of sucutaneous bronchial autografts. These autografts (12 to 14 per dog) became vasculari& and lined with normal respiratory epithelium. Four to 12 weeks after autografi implantation, 10% methylcholanthrene in crystalline form was put into 57 autografts and 10% methylcholanthrene in a silicone polymer sustained-release implant was placed into 54 autografts. Ten autografts without carcinogen (one per dog) served as controls. Serial samplingsofeachaulograftduring9to97 weeksofcarcinogenexposure showed the neoplastic progression from normal bronchial cells 10 invasive cancer through stages such as atypical squamous metaplasia and carcinoma in situ. To date, cancers have been histologically proved in 6Oautografts; 36 were induced by implants and 24 by the crystalline form. Thirty-nine cancers were epidcrmoid, and the remainder were either adenocarcinomas (n = 3) or poorly differentialed spindle cell cancers(n= l8).Thcsus~ined-releaseimplantmethodresultedinlarger autografts with a greater tendency to progress to cancer than the crystalline carcinogens (p > 0.025). Therefore, the sustained-release implant is now considered the preferred method. Measurement of nuclear dcoxyribonuclcic acid by image analysis of nine histologic cancers demonstrated hyperploidy. Deoxyribonucleic acid from the Ll repeated sequence family was demonstrably hypomethylaled in spindle cell tumors. Curettement of individual autografts yielded sheets of respiratorycpithelium from which43.5 to409.5 ??gofdeoxyribonucleic acid was isolated. For tbc first time, deoxyribonucleic acid from each stage of the neoplastic progression in non-small cell lung cancer is available in adequate quantities for serial biochemical and therapeutic analysis.
Effects of bombesin on growth of human small cell lung carcinoma in vivo. Alexander RW, Upp JR Jr. Poston GJ. Gupta V, Townsend CM Jr, Thompson JC. Department ofSurgery, The University ofTexmMedica1 Branch, Galveston, TX 77550. Cancer Res 1988;48:1439-41.
Bombesin-like peptides are found in many different human tumors and are thought to function as an autocrine growth factor for small cell lung cancer in humans. In this study, a human small cell lung carcinoma (NCl-H69)wass.c.implantedbilaterallyintotheflanksof 12nudemice. The mice were randomized an divided into two groups and given either bombesin (20 *g/kg) or saline i.p. 3 times a day. Tumor areas were measured twice weekly for 6 wk. At sacrifice, the tumors and noromal pancreas were excised, wcighcd, and assayed for DNA, RNA, and protein content. Significant stimulation of tumor growth was observed atwecks4.5.and6.Tumorweightatsacrifice wassignificantlyelevated (77%) above the control, as was DNA content (78%). Bombesin significantly increased the weight (42%). DNA (48%). and protein (61%) contents of the normal mouse pancreas. We conclude that bombcsin may act as an autocrine growth factor, or indireclly through therclcaseofotbcrgrowth factors,on human smallcell lungcarcinoma.
v-fps protein-tyrosine kinase coordinately enhances the malignancy and growth factor responsiveness of pre-neoplastic lung fibroblasts. Sadowski I, Pawson T, Lagardc A. Department of Medical Generics, University of Toronto, Toronlo, Ont. MSG 1X5. Oncogene 1988;2:241- 7.
Non-small cell lung cancer in autogenous subcutaneous bronchial grafts in dogs. Derrick MJ, Hammond WG, Pak HY, Azumi N, Smith SS, Benfield JR. Division ofSurgery, City ofllope Medical Center, Duarte, CA. J Thorac Cardiovasc Surg 1988;95:562-71.
The progression of preneoplasia into lung cancer can be serially
The v-fps oncoprolein was expressed in a pre-neoplastic, growth factor-depcndcntchincsc hamsterlungfibroblastline(CCL39)tostudy its effect on growth controls and on the induction of malignancy. Two Lransfcctanlswerecharacterizcdwhichexpressedlow(39FPS-8)orhigh (5lFPS-6) levels of P130(gag-fps) protein-tyrosine kinase activity. 39FPS8 cells still arrested in quiescence when deprived of growth factors, but developed an increased sensitivity to the mitogenic actions