Arylsulphatase and its relation to homovanillic acid in neuroblastomas

CCA 4860

Arylsulphatase

and its relation to homovanillic acid in neuroblastomas

Keuroblastomas, like malignant melanomas and the more benign ganglioneuromas and pheochromocytomas, are histogenetically derived from neural crest tissue. The four types of tumors produce catecholamines which are metabolized and excreted acid (VML4)1r2. I’ig. I in the urine as homovanillic acid (HVA) and/or vanillylmandelic summarises in a simplified manner some of the pathways for formation and metabolism of the phenylethyl amines in the above tumors. In a preliminary report we reported that there was an increased tumor content of the lysosomal enzyme arylsulphatase in melanomas~ ?,‘. K-e also observed that the degree of pigmentation and tyrosinase urine HVA concentration. However,

activit!- of the tumor is directl? there is an inverse relationslnp

related to the between the

urine HVA and urine arylsulphatase in melanomas. In amelanotic tumors the urine HVil is low or normal and the arylsulphatasc is elevated. In contrast, in melanoticvarieties, the urine H\‘A is elevated while the nr~.lsulphatase is normal to slightl> elevated”. It is not unusual to confuse neuroblastoma with other types of solid tumors (glioma, sarcoma, or lynpl~osarcoma)~~7. However, since the first report by Mason cdNI. in 1957 of increased levels of catecholamines in urine of a child with ncuroblastoma.

.

1 .g i;

40

-

30

-

z f

.

E 20

-

3 2

.

.

. ‘O-

0

.

IO

20

30

Aryfsulphotose

40

50

60

fmg/mf/br/

Fig. I. Correlation between HVA and arylsulphatase. lkch scissa) and arylsnlphatasc (coordinate) for a single patient.

dot represents

the urine

H\‘.A

(ab-

Case So.

numerous

similar

observations

have been reported

and urine catecholamines,

VMA

and HVA assays are useful in making a diagnosis1~8~9. To date, we have studied eight patients with neuroblastomas as well as hundreds of patients with melanomas. All had inverse ratios of urine arylsulphatase and HVA. Three of the neuroblastomas were initially diagnosed as a sarcoma, a lymphosarcoma, and an acute myelocytic leukemia, resp., and later found to have an inverse relationship between urine HVA and arylsulphatase (Fig. I and Table I). The HVA and arylsulphatase were assayed according to the procedures previously describedlO,ll. The assay does not attempt to differentiate the A and B isoenzymes of arylsulphatasel”. Only in patients No. I, 3, 6, 7, 8 were the urine VMA values elevated (greater than IO mg per 24 h). The one exception seen in Fig. I and Table I was a patient (No. 2) with extensive liver metastasis and necrosis perhaps accounting for the elevated arylsulphatase13. Fig. 2 is an attempt to interpret the relationship between HVA and the enzyme arylsulphatase. Phenylalanme -Ty’olsi”e

b- Melanin

DOPA ];-NTNDjAN-

3- methoxy

DA

\ 3,4-dihydroxy phenylacetic acid

Adenylic sulphote Sulphotinp Enzymes Adenylic acid x ABBREVIATIONS:

I:&.

L. httempt

V,

HVA HVA

DOPA: 3,4_dihydroxyphenylalanine DA:

3,4-dihydraxyphenylethylamine (Dapamine)

DLA: NE: E:

3,4-d~hydraxyphenyllactic Norepinephrine Eplnephrine

to relate

tyrosinase

sulphate ,,c

NMN: MN: MPS: MHPG : VMA: HVA:

acid

Inetabolisrn

MPS sulphates rylsul/bahw MPS

A

with

Normetanephrine Metanephrine Macapolysaccharide Methaayhydroryphenylqlycal Vanilylmandelic acid Homavanillic acid

arylsulphatase

activity.

BRIEF

294 LArylsulphatase is present

SOTES

in all tissues and elevated in most visceral neoplasms

(refs. 4,13). However, the elevated concentrations of DOPA and HVA produced by the neuroblastoma cell system, which are excreted in part as sulphates, could keep the enzyme localized within the tumor (stabilization of lysosomal membrane). In the prcsence of low to normal HI’A the enzyme is released and excreted in the urine”. Sonic feel that arylsulphatase may supply active sulpliate via arylsulphatasc action to carlxhydrates (Suzuki ct al.lj). The resulting carbohydrate sulphates would be a r-eatl!. substrate for the increased mucopolysaccharide sulphates that are present in mclanc~mas and neuroblastomasl~.

(I) Urine arylsulphatase and HVA have been found to be inverselv related in patients with neuroblastomas. (2) By quantitative methods urinary excretion of H\‘A was found to be elevated in all our patients with neuroblastomas even when IMA was

not elevated. These results seem to indicate that the relationship between melanin metabolism and the hydrolytic enzymes is also applicable to the neuroblastomas and suggests that arylsulphatase assays might be a useful supplement to the routine tests for mela nogens. ACKNOWLEDGEMENTS

Cancer

Supported Institute,

by Grants Bethesda,

Numbers CA-05108, Maryland, U.S.A.

CA-05837

6 H. HUTCHISOS, Quart. J. Med., I (1907) 33. 7 W. PEPPER, AWPY. ,/.:\led. scz., 121 (1901) 287. 8 G. h. &IASOS, J. HART-bIERcER, E. J. ibIILLER,L. B. STRANG (19.57) 322. 9 S. E. GITLOW,

L. M. BERTASI,

A. RACSEN,

D. GRIBETZ

AND

and CA-08087,

National

ASII s. \I\:YssE,~a~zcc~t, ii S. W.

DZIE~ZI~, Cazccr, 2.5

(1970) 377. in press. II L. Ii.MORCA~;, T3.Mhvr)ux, M. S. S.cvmELs *ND E. T. KREMENTZ, Canccv, Submitted. 12 H. BAUM, K. S. DODGSON .4ixi~ B. SPESCER, CZi?z.Chim. Acta, 1 (Ig_j9) 453. B. Mmuux, L. RODRIGUEZ, G. GIDMM, IN.S. SAIWELS 13 L. R. MORGAS, N. J. REEHLMANS, ASD 1:.T. KREME~TZ, CZin. Chim. Acta, 32 (1971) 316. rq I,.Ti.MORGAN, M. S. SAMUELS AND E. T. KREMENTZ, unpnblished. 1.5 S. SUZCKI, N. TAICAHASHI AND I;.EGAMI, Biochim.Baophys. Acta, 24 (1957) 444. CZin. Chin?. Acta,

37 (1972)

292-29,