Chromogranin A alters ductal morphogenesis and increases deposition of basement membrane components by mammary epithelial cells in vitro

The extracellular function of chromogranin A (CgA), a glycoprotein widely d istributed in secretory vesicles of neurons and neuroendocrine cells, has n ot been clearly established. To examine whether CgA might modulate the biol ogical properties of epithelial cells, we used an in vitro model of ductal morphogenesis in which mammary epithelial (TAC-2) cells are grown in three- dimensional collagen gels. Whereas under control conditions TAC-2 cells for med thin, branched cords with pointed ends, in the presence of CgA they for med thicker cords with bulbous extremities, reminiscent of growing mammary ducts in vivo. Immunofluorescence analysis demonstrated that CgA increases the deposition of three major basement membrane components, i.e., collagen type IV,laminin, and perlecan, around the surface of the duct-like structur es. Similar effects were observed with CgA partially digested with endoprot einase Lys-C, suggesting that one or more fragments of CgA are endowed with the same activity. These findings reveal a hitherto unsuspected activity f or CgA, i.e., the ability to alter ductal morphogenesis and to promote base ment membrane deposition in mammary epithelial cells. (C) 1999 Academic Pre ss.