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pCi (880 cGy of wholcbody radiation). As anticipated, a muhiple-dose regimenof49OpCi in fourdoscsover lOdays (720cGyof whole-body radiation, eight of eight surviving >30 days) was less toxic than a single bolus dose of 430 pCi (644 cGy of whole-body radiation), six of eight surviving >30 days). A muhidose radioimmunotherapy regimen was initiated in nude mice bearing 66-mm’ tumors (total dose, 500 to 600 pa). Complete remissions (>I40 days) were achieved in three of 16 mice, and the remainder showed a mean iumor growth delay of 53 days. Matched doses with irrelevam MAb produced one remission, one treatment-related death, and a mean growth delay of only 20 days in six of eight mice. Thus. in this nonoptimal radioimmunotherapy model. significant antitumor responses were observed using a mildly toxic multiple dosing regimen.

Theeffectsoffive hematopoieticgrowthfactorson humansmallcell lung carcinoma cell lines: Interteukin 3 enhances the proliferation in one of the eleven cell lines Vellenga E. Biesma B, Meyer C. Wagteveld L, Esselink M, De Vries EGE. Department of Hematology, University Hospiral. Oostersingel

59,9713 EZ Groningen. Cancer Res 1991;51:73-6. Eleven small cell lung carcinoma cell lines of human origin were

exposed to different colony stimulating factors (CSFs) to study whether CSFs could enhance the spontaneous cell proliferation and modify the action of cytotoxic drugs. In ten cell lines no suppressive or stimulalive effect was observed when measured in a [‘Hlthymidine assay and a 3(4,5-dimethylthiaol-2-yl)-2.5-diphenyltetrazolium bromide assay. However, one cell line (GLC-20) could be s1imulated by mterleukin 3 (IL-3)whenmeasuredwithaproliferativeaswellasaclonogenicassay. This enhancing effect was cell concentration dependent in the ?Hlthymidine assay. Addilional CSFs such as granulocyte-macroph- age-CSF, granulocyte-CSF, IL-4. IL-6, insulin, or bombesin could not further augmcm the IL-3 supported proliferation. In addition, IL-3 binding studies demonstrated the presence of IL-3 receptors on the GLC-20 cells. Two types of receptors were demonstrated by Scatchard analysis: high affinity receptors (59 f 4 sites/cell) with a dissociation constant (K(d)) of 3 I f 9 pmol/liter; and low affinity receptors (I915 f 91 sites/cell) with a K(d) of 2.0 f 0.8 nmol/hter. Finally, it was shown tha1 the toxic effecls ofadriamycm and cisplatin on the proliferatton of the GLC-20 cell line could partially be abrogaled in the presence of IL- 3. These data indicate that in some cases CSFs can modulate the proliferation of small cell lung carcmoma ccl1 lines and Interfere with the effects of chemotherapeutic drugs.

Characterization of VIP- and helodermin-preferring receptors on human small cell lung carcinoma cell lines Luis J, Said SI. Universily of Illinois. Chicago, IL 60612. Peptides 1990;11:123944.

We investigated the molecular and pharmacologic characteristics of VIP receptors on two human SCLC cell lines: NCI-N592 and NCI- H345. With NCI-N592 cell, the order of potency of VIP-related pep- tides in inhibiting ‘?-VIP binding and in stimulating CAMP production wastypicalofthe human VIPreceptor. Bycovalentcross-linking,apol- ypeptide of Mt 62,300 was obtained. Conversely, the behavior of NCI- H34S cell line was lotally different: helodermin was the most potent peptide, VIP and PHI were equipo1ent. while hGRF and secretin were totally ineffective. These resul1s suggest that NCI-N592 cells possess a lypical VIP receptor while NCI-H345 cells possess a helodermin- preferring receptor, and tha1 the na1ural target of helodermin might not bc the VIP receptor.

Vasoactive intestinal polypeptide binds with high affinity to non- small cell lung cancer cells and elevates cyclic AMP levels Lee M, Jensen RT, Huang SC, Bepler G. Korman L, Moody TW. Deparrmem ofBiochemisrry and Molecular Biology, George Washing- [on University School of Medicine and Health Sciences. 2300 Eye St.

N.W.. Washington. DC 20037. Peptides 1990;11:1205-9. Vasoactive intestinal polypeplidc (VIP) receptors were character-

ized on non-small cell lung cancer (NSCLC) cells. ‘“I-VIP bound specilrcally to membranes derived from 6 NSCLC cell lines. Specific

12JI-VIP was time dependent and a linear function of EPLC-65H membraneconcentration. ‘UI-VIPbound with high (K(d)=0.2nM)and moderate (K(d) = 39 nM) affinity to two classes of sites. Pharmacology studies indicated mat the order of peptide potency was VIP > rGHRH > PHI = helodermin > secretin > glucagon. Also VIP elevated the CAMP levels IO-fold using cell line ADLC-5M2. These data indicate 1hat functional VIP receptors are present on NSCLC cells.

Cell-surface antigens of human lung tumors detected by mouse monoclonal antibodies: Definition of blood-group- and non-blcod- group-related antigenie systems Feicken H-J, Anger BR, Cordon-Cardo C, Lloyd KO. Memorial Sloan- Keffering Cancer Center. 127s York Avenue. New York. NY. Int J Cancer 1990;46: 1007-13.

The pattern of antigen expression in human non-small-cell cancers of various histiological subtypes has been studied. Mouse monoclonal antibodies (MAbs) were generated following immunizations with cell lines of squamous, adeno- and anaplastic large-cell carcinomas of the lung. Seven non-blood-group-related antigens were defined in addition to 5 antigens related to blood-group determinants. Detailed specificity was established with a large panel of cultured cell lines and normal and neoplastic tissues. MAb F-18 reacted in direct tests with the immuniz- ing squamous lung carcinomacell line, with 5 out of 5 choriocarcinoma celllines,butwithnoothercellItnes. NoexpressionofF-18antigenwas observed in any normal or malignant tissue examined. The other6 non- blood-group-reactiveMAbs(F-7,F-8,F-Il,F-15,F-16andF-17)could be distinguished by their reactivity on a panel of cultured cells and tissues. One MAb in this group (F-17) reacted strongly with 1905 lung tumor cell lines, 32116 other tumor-derived cell lines, cultured normal kidney cells and fetal lung fibroblasts. This antibody did not react with any normal adult tissues examined, but did react with several cancer tissues including l/l7 lung tumors, 2/4 ovarian cancers and l/S colon tumors. Immunoprecipilation tests revealed that 5 of theantigens were glycoproteins: F-18 (M(r) > 200,000). F-15 (M(r) 44,ooO). F-16 (M(r) ~,~),F-l7(M(r)95,000)andF-8(M(r)95,000).FourMAbsdetecled Y blood-groupandgen &e(y)), only 2 of which wereable toagglutinate 0 erythrocytes. Another antibody detected X blood-group antigen &e(x)).

An adherent subline of a unique small-cell lung cancer cell line downregulates antigens of the neural cell adhesion molecule Doyle LA, Barges M, Hussain A, Elias A. Tomiyasu T. University of Maryland Cancer Center, Umvcrsity of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD 21201. J Clin Invest 1990$6:1848- 54.

Small-cell lung cancer (SCLC) lines are distinguished from non- small-cell lung cancer (NSCLC) lines by their growth in floating aggregates, in contrast 10 Ihe adherent monolayers formed by NSCLC cells in culture. Of 50 well-characterized SCLC lines recently described by the National Cancer Instiuae (NC&Navy Medical ticology Branch. only four variant cell lines (SCLC-v) grew as adherent monolayers. Ch-ie line. NCI-H446. was unique in growing long-term with coexisting floating and surface adherent subpopulations. We have physically segregated these two populations over many passages in vitro to enrich forrelativelypureculturesoffloatingandadherentcells. Nodifferences in c-myc expression, kcratin pattern, or cytogenetic appearance were found between the adherent and floating sublines. However, expression of the neuroendocrine marker neuron-specific enolase in the floating cells was three times that found in the adherent cells. The floating subline also had much greater surface expression of neuroendocrine tumor antigens detected by monoclonal antibodies UJ l3A and HNK- I, which have been recently shown 10 detect the neural cell adhesion molecule (NCAM) on SCLC cells. Two other adherent SCLC-v lines were also found to be unreacrive with UJ13A and HNK-I, generalizing the association between NCAM expression and the growth of most SCLC cultures as flonmg aggregates. In conclusion. we have an interesting model to study cxprcssion of NCAM as related to the adhesive properties of SCLC cells.