Human breast carcinoma slice cultures retain retinoic acid sensitivity

We have shown earlier that surgical human breast cancer tissue can be maintained in culture as intact tissue slices (organ culture). Because tumor organ culture ostensibly preserves the interacting network of tumor cells, stromal fibroblasts, endothelial cells and extracellular matrix, it represents a rather complex culture system. Such a system may be especially useful in preclinical trials, where the objective is to make extrapolations to the even more complex in vivo situation. A classical therapeutic target in breast cancer is the estrogen receptor, and we showed earlier that human breast cancer slices retain expression of this receptor in culture. Retinoic acid, the active form of vitamin A, is also an important (negative) growth regulator in breast cancer. In the present communication, we used in situ hybridization to monitor the expression of retinoic acid receptors in tumor slices cultured for 4 days. We show that both members of the all-trans retinoic acid and 9-cis retinoic acid receptor family (RAR and RXR, respectively) are expressed. Moreover, RNase protection analysis showed that expression of the cellular retinoic acid-binding protein type II gene, a known retinoic acid target gene, is upregulated by treatment with 1 μM all-trans retinoic acid for 2 days. These findings attest to the feasibility of using tumor organ cultures as a preclinical model for the evaluation of synthetic vitamin A derivatives (retinoids).