EFFECTS OF LINOLEIC-ACID ON THE GROWTH AND METASTASIS OF 2 HUMAN BREAST-CANCER CELL-LINES IN NUDE-MICE AND THE INVASIVE CAPACITY OF THESE CELL-LINES IN-VITRO

The purpose of the study was to compare the effects of dietary linolei c acid (LA) intake on the growth and metastasis of MDA-MB-435 and MDA- MB-231 human breast cancer cells in nude mice, together with their inv asive capacity and secretion of type TV collagenase (gelatinase) ill v itro, Each tumor cell line (10(6) cells) was injected into a right-sid ed mammary fat pad in 60 mice with equal numbers (30 mice/group) assig ned to isocaloric diets containing 23% (w/w) total fat and 2% or 12% ( w/w) LA, The MDA-MB-435-cell mammary fat pad tumors became palpable ea rlier and initially they grew more rapidly, but by 6 weeks the MDA-MB- 231-cell tumors exhibited an acceleration of growth which was enhanced by the high-LA diet, At necropsy, 12 weeks after the tumor cell injec tions, the mean weight [10.2 +/- 1.4 g(SEM)] of mammary fat pad MDA-MB -231 cell tumors in 12% LA-fed mice was significantly higher (6.7 +/- 1.4 g) than that of the mice fed 2% LA; also, it was higher than that of MDA-MB-435 cell tumors in the 12% LA fed mice (3.6 +/- 0.1 g) or th e 2% LA-fed mice (3.3 +/- 0.1 g) (each P < 0.001). Mice fed the 12% LA diet had a higher incidence of grossly visible MDA-MB-435 cell pulmon ary metastatic nodules than those fed the 2% LA diet (67% versus 33%; P < 0.02), more metastatic lesions (5.7 +/- 1.6 versus 2.3 +/- 0.8; P < 0.05), and greater total volumes (62.0 +/- 25.9 versus 24.8 +/- 9.0 mm(3); P < 0.02) per mouse, Of the MDA-MB-231 cell tumor-bearing mice, only 1 in the 12% LA dietary group and 2 in the 2% LA dietary group h ad macroscopic nodules but the incidence of microscopic metastases was 68 and 42%, respectively, The MDA-MB-231 cell line exhibited a relati vely high capacity for invasion in vitro and constitutively high level s of both total type IV collagenolytic activity and M(r) 92,000 gelati nase production which were unaffected by LA, In contrast, MDA-MB-435 c ells had approximately only one-sixth the invasive capacity and secret ed a relatively low level of type TV collagenase and little of the M(r ) 92,000 gelatinase; both invasion and enzyme production were stimulat ed by LA,