187

TNF-a (EC,,: 2.7, 8.2, and 2.4 pM, respectively), although a series of

othercylokinesandgrowth factors didnol have thiseffecl.Cort& also

increased 13AR density (EC,,: 30 nM) and markedly porentiated the

effects of IL-la, IL-U, and TN&a. Neither IL-1 nor cortisol influ-

enced Lhe. proportion of cell surface vs internalized BAR. The IL-l-

induced increase in BAR density was half-maximal after 6 h, was

reversible at a similar rate, and was blocked by I pM of cyclohcximide.

The effect of IL- 1 on LIAR was specific, as the density of glucocorticold

receptors, measurement by 3H-dexamethasone binding, was reduced by

IL-I. Both conisol and IL-1 potentiated the isoprolerenol-induced

mcrease in CAMP accumulation. IL-1 Inhibited cell proliferation and

thymidine uptake, and mcreased the adherence of A549 cells to the

plasticcultureflask,asquantifiedbyacellderachmen~assay.Theeffect

of IL-1 on cell adherence was not inhibited by cycloheximide. Cortisol

decreased cell adherence and prevented Ihe IL-l-induced increase m

adherence. Theresults Indicate that multiplceffectsofIL-1 inacultured

tumor cell line involve different mechanisms, suggesting heterogeneity

of IL- 1 R and/or coupling of IL- 1 R 10 distinct, nuclear, and nonnuclear,

effector pathways.

A human monocyte growth factor produced by lung cancer cells

Okabe T, Yasukawa K. The Third Deparmznf of Internal Medicine, Facuify of Medicme. Universilj of Tokyo, llongn 7-3-l. Bunkyo-ku. Tokyo 113. Cancer Res 1990;50:3863-5.

Human lung cancer cell lint, T3M.30, has been shown io produce a

growth factor that stimulalcs problcratlon of peripheral blood mon-

wyles. In Ihe prescncc of this factor, human circuladng monocyles

were able Lo prolifcratc in wuo. Gel exclusion chromatography of Ihe

condrlioned medium rcvealcd a smgle peak of monocyte growth-pro-

motingactlvi~ya~anapparentmolccularwcigh~of 16,OOO.Thegrowth-

promoting activity was absorbed to an anion-exchange column, Mono

Q, and clutcd wlh a salt gradlcnc as a single peak of bioactivity at 300

mM NaCI. When the sample was applied to a Vydac C, column, a

rcversc-phase ixgh-pcrformaoce liquid chmma~ogrdphy column, a single

peak of activity was observed at a concemration of 76% acetonilrile in

0.1% Uifluoroacctic acid. The monocytc growth-promoting activity

was heat stable at 56°C. 11 was partmlly dcsuoyed by trypsin. The

activity was lost alLr trcatmcnt with 2.mcrcapmethanol.

Aneoropeptideantagonist that inhibits thegrowthofsmallcelllung

cancer in vitro

Wall PI, Rozengurl E. GrowrhRegularionLaboratory,lmperral Cancer Research Fund. Lmcoln’s Inn Fields, London WCZA 3PX. Cancer Rcs

1990;50:3968-73.

In Ihe search for novel antlprobfcrative agenE for small cell lung

cancer (SCLC), WC found the ncuropeptide anragomst [Arg6,D-

Trp’~‘,MePheR]subscance P(6-I I) to be effective in vitro. In “urine

Swiss 3T3 cells [Arg6,D-Trp7,9.MePheR]subsllnce P(6-11) was identi-

fled as a potcnt inhibitor of vasoprcssin-stimulated DNA synthesis

whrch also blocks [‘Hlvasopressm bmding to spwfic cell-surface

rcceplors. It was a less potent antagonist of gastrin-releasing pcptidc

and bradykinin in these cells but did not block Ihe effects of other

mllogens. In SCLC cell lines, [Arg”.D-Trp7~P,MePheR]subslance P(6-

I I) inhibltcd colony-formauon in soft agarosc and growth in hquid

cullurc in a dose-dependent manner. It also blocked rcccplor-mediated

Ca” mobibzatlon induced by vasopressm, bradykinin. cholecystokinin,

galanin, gasuin-releasing pepudc, and ncurownsm. We suggest that

broad-specuum neuropcptide antagonists can block multiple autocrinc

and paracrinc growth leaps m SCLC and could bc useful therapeutic

agents.

Cloned low m&static variants from human lung carcinoma metas- tases

Varki NM, Tseng A, Vu TP, Estcs LA. Deparlmenl ofMedicine, Cancer Cenrer. Universify of Califorma. San Diego, La Jolla. CA 92093.

Anticancer Res 1990;10:637.43.

ClonaI subpopulations of neoplasuc cells were derived. in soft agar,

from the spontaneously metastazrng variant (MV522) of a human lung

carcinoma cell line. The ability of these clones 10 spontaneously

mciastasiz from subcwmcous sites m athymic mlcc was then tested. A

variation m mctastatic ability was cxpecwd with tic derivation ofsomc

low mctascalic clones and some high mcliL\taUc ones. However, all of

the denvcd clones, although equally tumortgemc, were less metasIatic

than Ihe parental variant. Thcsc clonal ccl1 lines can now be used in a

syslemaw analysis of cvcms asssoclatcd with Ihc reversion 10 a Icss

malignant staw.

Retinoic acid and epidermal growth factor binding in retinoid-

mediated invasion suppressed human lung carcinoma cells

Fazely F, Lcdinko N. Dana-Farber Cancer Research Inslr~ule, 44 Binnq Swea, Bosmn, MA 021 IS. Amicanccr Rcs 1990;10:667-70.

The cffcct of rctinolc acid (RA)-mduccd suppression of m wtro

mvasivc abUy of A549 human lung carcinoma cells on cellular

bmdingofRAand cpidcrmalgrowh faclor(EGF) was mvcs~lgawd.RA

inhibitloo of cell invasive potcmlal was accompamcd by a slgmficam

increase m specific hrgh affmity ceilular rctmoic acid bindmg protein

(CRABP) Icvcl. An approxlmalcly 2.7.fold mcreasc in cytosolic CRABP

was found in RA-trcawd cells (450 fm/mg prolem compared Lo I67 fm/

mg comrol cell protein). In conwarl, ‘“51-EGFligand hmmg was slmdar

for corm01 and ucatcd cells.

Expression of CYPlAl gene in patients with long cancer: Evidence

for cigarette smoke-induced gene expression in normal long tissue

and for altered gene regulation in primary pulmonary carcinomas

McLcmorc TL, Adclbcrg S, IJU MC cL al. Program Deve~opmenr Research Group. Developmental Therapeulics Program. Division of Cancer 7’reuumxl. Na~uvzul Cancer In,wuie, Bahesda, MD. J Nat1

Cancer Inst 1990 82:1333-Y.

The major polycyclic ammaw hydrocarbon mduclblc-cytochrome

P4501Al gene (CYPIAI) is prcsumcd Lo be imporlanr in pulmonary

carcinogcncsls and loxlcology because its product, the cyuxhrome

P450lAl -dependent (CYPlAl-dcpcndcnl) monooxygenasc, transforms

selected xenoblotics (including polycyclic aromatic hydrocarbon pro-

carcmogcns in clgarcllc smoke) Lo potent carcmogcmc mctabohles.

CYPIAI messenger RNA (“RNA) cxprcss~on has not, howcvcr, been

previously demonstrated m human pulmonary IISFUC. This report dc-

fines CYPIAI gene cxprcssion m normal lung twuc and primary

pulmonary carcmoma wsuc oblaincd at lhoracolomy from 56 paticms

with lung cancer. When Northcm blor hybridwation analysts were

pcrformcd,l7ofl9(X9~)and~crooff~vc(O%~samplcvofnormallung

lissuc from actwc cigaretlc smokers and nonsmokers, rcspcchvcly.

cxprcsscdthcnormal2.&ktlobascCYPl Al “RNA. Inaddlrmn,atrmc-

dependent dccrcasc m cxprcssmn of the CYPIAI gene was noted m

normal lung tissue from indiwduals who wcrc lormcr smokers, with a

decreascmcxprcssionoccurringascarlyas2 wccksfollowlngccssauon

of cigarcue smoking. Expression bccamc undcrcctablc m all patients

who had slopped smokmg mom than 6 weeks prior Lo study. When

CYPI A 1 gcnc cxprcsslon was cvaluatcd in lung cancers, mRNA levels

were delcctablc m one of four (25%) tumors from nonsmokers; two of

24 (8%) tumors from former smokers; and sewn of 15 (47%) tumors

from cigarctlc smokers. In addition, an approximately IO-kilobasc

CYPIAI RNA spccles, whvzh was not delectable m normal lung tissue,

was obscrvcd in fwc of ten (50%) of the lung cancers that cxprcssed Ihe

CYPIAI gcnc. There was no pasmvc assoclauon bcwcen CYPl Al

cnpression and lung cancer hwologic cell type nor bctwccn CYPl Al

“RNA lcvcls m malchcd normal lung ussuc and tumor Llssuc from

pauents with lungcanccr. Thcscrcsullsdcmonslratcaposlclvcassocla-

lion bctwccn acwc clgarcw smoking and CYPI Al gene expression m

normal human lung tissue. Morcovcr, CYPIAI gcnc exprcsslon was

documcntcd m many pulmonary carcmomas, and altered rcgula~ion of Ihc gene was also obscrvcd m scvcral lung tumor?.

Short- and long-term synergistic effects of human tumor necrosis

factor and interferon-gamma on AS49 human lung cancer cells

maintained in three-dimensional culture

Beaupain R, Martyre MC. Laboraloire d’lmmunopharmacologie Ex- perimenrale. UPR-405 CNRS. 15 Rue de I’Ecole de Medecine. 75270 Paris Cedex 06. Anticancer Res 199O;lO: 1061-6.