Proliferation and survival of mammary carcinoma cells are influenced by culture conditions used for ex vivo expansion of CD34(+) blood progenitor cells

Malignant cell contamination in autologous transplants is a potential origi n of tumor relapse. Ex vivo expansion of CD34(+) blood progenitor cells (BP C) has been proposed as a tool to eliminate tumor cells from autografts. To characterize the influence of culture conditions on survival, growth, and clonogenicity of malignant cells, we isolated primary mammary carcinoma cel ls from pleural effusions and ascites of patients with metastatic breast ca ncer and cultured them in the presence of stem cell factor (SCF), interleuk in-1 beta (IL-1 beta), IL-3, IL-6, and erythropoietin (EPO), ie, conditions previously shown to allow efficient ex vivo expansion of CD34(+) BPC. In t he presence of serum, tumor cells proliferated during a 7-day culture perio d and no significant growth-modulatory effect was attributable to the prese nce of hematopoietic growth factors. When transforming growth factor-beta 1 (TGF-beta 1) was added to these cultures, proliferation of breast cancer ce lls was reduced. Expansion of clonogenic tumor cells was seen in the presen ce of SCF + IL-1 beta + IL-3 + IL-6 + EPO, but was suppressed by TGF-beta 1 . Cocultures of tumor cells in direct cellular contact with hematopoietic c ells showed that tumor cell growth could be stimulated by ex vivo expanded hematopoietic cells at high cell densities (5 x 10(5)/mL). In contrast, cul ture under serum-free conditions resulted in death of greater than 90% of b reast cancer cells within 7 days and a further decrease in tumor cell numbe rs thereafter. In the serum-free cultures, hematopoietic cytokines and cell ular contact with CD34(+) BPC could not protect the tumor cells from death. Therefore, ex vivo expansion of CD34(+) BPC in serum-free medium provides an environment for efficient purging of contaminating mammary carcinoma cel ls. These results have clinical significance for future protocols in autolo gous progenitor cell transplantation in cancer patients. (C) 1999 by The Am erican Society of Hematology.