Investigation of the growth and metastasis of malignant melanoma in a murine model: the role of supplemental vitamin A

Vitamin A possesses both wound-healing and antitumor actions. Vitamin A-induced fibroplasia results in subsequent increased collagen production and deposition. This effect of vitamin A has been shown to result in the production of collagenous capsules around several murine breast and lung tumor systems. This tumor encapsulation process can potentially convert a systemic disease to a local one that can be easily treated by tumor excision. The goal of the present study was to determine whether supplemental vitamin A could promote the encapsulation of a murine melanoma. Sixty DBA/2J male mice were inoculated intracutaneously with 1 x 106 Cloudman S91 melanoma cells using a 30-gauge needle. The mice were divided into three groups: a control group, a pre-vitamin A group, and a post-vitamin A group. The control mice were fed a commercial chow containing 15,000 IU of vitamin A and 6.4 mg of beta-carotene per kilogram diet, considerably more than the National Research Council's recommended daily allowance of vitamin A for normal mice. The control diet was, therefore, not vitamin A-deficient. The pre-vitamin A mice were fed the basal chow supplemented with 150,000 IU of vitamin A per kilogram diet for 10 days before inoculation and for the remainder of the study. The post-vitamin A mice were fed the vitamin A-supplemented diet beginning on the day of inoculation and continuing for the remainder of the study. Sixty days after inoculation, tumor growth was assessed and the five mice remaining in each group were euthanized. Ventral skin at the site of inoculation was harvested for histologic assessment of local tumor growth and invasiveness. The liver and lungs of each of these mice were also harvested for histologic assessment of tumor metastasis.Sixty days after tumor inoculation, a 60 percent survival rate was observed in the control group as opposed to the vitamin A-supplemented animals, which demonstrated a 100 percent survival rate in both groups (n = 5 in each group). Decreased mean tumor size and gross tumor in most vitamin A-supplemented animals were statistically significant when compared with the control animals. The control animals had a mean tumor size of 26.1 mm, whereas the post-vitamin A group had a mean tumor size of 5.7 mm. One hundred percent of the control group exhibited tumor; one animal had distant metastases. The pre-vitamin A group did not exhibit any tumor growth, and the post-vitamin A group exhibited tumor growth in 40 percent of animals. Neither vitamin A-supplemented group showed any evidence of distant metastases. The animals supplemented with vitamin A demonstrated decreased tumor growth and metastasis. This in vivo model may indicate a potential prophylactic and therapeutic role for supplemental vitamin A in the treatment of malignant melanoma.