Effect of Dietary Fat on Human Breast Cancer Growth and Lung Metastasis in Nude Mice

Abstract

Results from epidemiological studies have generally indicated an association of dietary saturated animal fats with human breast cancer risk. Some studies, however, have suggested a similar association for some polyunsaturated vegetable fats shown to promote both rodent mammary carcinogenesis and metastasis. This study was performed to evaluate the effects of corn oil on growth and metastasis of MDA-MB-435 human breast cancer cells, which have a propensity for metastasis. Corn oil is rich in the omega-6 fatty acid linoleic acid. Fifty-eight female athymic nude mice (NCr-nu/nu) were fed a high-fat diet (23% wt/wt corn oil; 12% linoleic acid) or a low-fat diet (5% wt/wt corn oil; 2.7% linoleic acid). Seven days after diets were started, tumor cells (1 x 10(6) were injected into a mammary fat pad. The time to appearance of solid tumors and the tumor size were recorded. After 15 weeks, the study was terminated, and autopsies were performed to determine the weight of the primary tumor and the extent of metastasis. The latent interval for tumor appearance in the animals fed the high-fat diet was shorter than that in the low-fat diet group, and the tumor growth rate in the high-fat diet group showed a small but statistically significant increase compared with the low-fat diet group. Primary tumors developed in 27 of the 29 mice on the high-fat diet and in 21 of the 29 on the low-fat diet. Of the mice with palpable primary tumors, 18 of 27 in the high-fat diet group and eight of 21 in the low-fat diet group had macroscopic lung metastases. The extent of metastasis in the high-fat diet group was independent of the primary tumor weight, but only those in the low-fat diet group with primary tumors weighing more than 2 g developed metastases. These results suggest that a high-fat diet rich in omega-6 polyunsaturated fatty acid can enhance metastasis of human breast cancer cells in this mouse model. The findings support the need for further study of the relationship between dietary polyunsaturated fats and breast cancer risk and for experiments to determine the effect on metastasis of only a 50% difference in fat intake--the dietary goal of the proposed clinical trials of low-fat dietary intervention in breast cancer patients.

Mevalonate Promotes the Growth of Tumors Derived from Human Cancer Cells in Vivo and Stimulates Proliferation in Vitro with Enhanced Cyclin-dependent Kinase-2 Activity

“…Mice were housed in microisolator cages with sterile bedding and were handled in a unidirectional laminar airflow hood. They were maintained throughout the study on a standard AIN-93G diet (Dyets, Bethlehem, PA) that was sterilized by exposure to 60 Co (Steris Isomedix, Whitby, Ontario, Canada) (28). The tumor cell inoculation procedure has been described in detail elsewhere (27).…”

“…Briefly, cells were grown to 70 -90% confluence, and the medium was changed 24 h prior to harvesting by trypsinization. The cells were resuspended in complete medium and kept on ice prior to use (28). Under ketamine/xylazine anesthesia, mice received a small incision (1-2 mm) to expose the right thoracic mammary fat pad.…”

“…Fifty l of inoculum containing 10 6 cells were injected, and the wound was closed with tissue glue. Only those mice that developed a palpable, growing tumor were included in final analyses (28). One week later, under ketamine/xylazine anesthesia, mice were subcutaneously implanted with 200-l miniosmotic pumps (flow rate 0.25 l/h, 28-day pumping life) (Alzet Corp., Palo Alto, CA) in the intrascapular area and then randomized to two groups.…”

“…To this end, 40 female nude mice were inoculated with MDA-MB-435 cells and then randomized and implanted with miniosmotic pumps that provided a continuous supply of either mevalonate or saline (control). Thirteen mice in each group developed growing, palpable tumors, and only these mice were included in tumor measurements (28). Accelerated tumor growth in the mevalonatetreated animals was measurable after 7 weeks (Fig.…”

The embedded tumour: host physiology is important for the evaluation of tumour growth

“…Popp et al (1983) said that 'the goal of nutritional therapy in the tumour-bearing host is support of the host carcass in the absence of increased tumour growth.' Different food intake manipulations can be analysed with aid of our model, to figure out which manipulation may achieve that goal.Several authors discussed the possible benefits of a low-fat dietary intervention in cancer patients (Rose et al, 1991;Mukherjee et al, 2002). As both tumour and host may grow slower or even shrink as a response to the decreased caloric intake, the main issue is whether the tumour or the host suffers more from the effects of caloric restriction.…”