Physical transfer of membrane and cytoplasmic components as a general mechanism of cell-cell communication.

Recent evidence from different research areas has revealed a novel mechanism of cell-cell communication by spontaneous intercellular transfer of cellular components (ICT). Here we studied this phenomenon by co-culturing different cells that contain distinct levels of proteins or markers for the plasma membrane or cytoplasm. We found that a variety of transmembrane proteins are transferable between multiple cell types. Membrane lipids also show a high efficiency of intercellular transfer. Size-dependent cytoplasmic transfer allows exchange of cytoplasmic macromolecules up to 40 kDa between somatic cells, and up to 2000 kDa between uncommitted human precursor cells and human umbilical vein endothelial cells. Protein transfer, lipid transfer and cytoplasmic component transfer can occur simultaneously and all require direct cell-cell contact. Analyses of the properties of ICT, together with a close examination of cell-cell interactions, suggest that the spontaneous ICT of different cellular components might have a common underlying process: transient local membrane fusions formed when neighboring cells undergo close cell-cell contact.

Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells.

The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in many tumor types. Here, we report intercellular transfer of functional P-gp from P-gp-positive to P-gp-negative cells in vitro and in vivo. The expression of acquired P-gp is transient in isolated cells but persists in the presence of P-gp-positive cells or under the selective pressure of colchicine. The intercellular transfer of functional P-gp occurs between different tumor cell types and results in increased drug resistance both in vitro and in vivo. Most importantly, the acquired resistance permits tumor cells to survive potentially toxic drug concentrations long enough to develop intrinsic P-gp-mediated resistance. P-gp transfer also occurs to putative components of tumor stroma, such as fibroblasts, raising the possibility that multidrug resistance could be conferred by resistant tumor cells to critical stromal elements within the tumor mass. This is the first report, to our knowledge, that a protein transferred between cells retains its function and confers a complex biologic property upon the recipient cell. These findings have important implications for proteomic analyses in tumor samples and resistance to cancer therapy.