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Extracellular matrix regulation of PTHrP and PTH/PTHrP receptor in a human breast cancer cell line
Author(s) -
Luparello Claudio,
Schilling Tobias,
Cirincione Rosalia,
Pucci-Minafra Ida
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01635-x
Subject(s) - extracellular matrix , extracellular , cancer research , medicine , breast cancer , receptor , endocrinology , cell culture , chemistry , microbiology and biotechnology , cancer , biology , genetics
It was previously reported that 8701‐BC breast cancer cells express the gene for parathyroid hormone‐related peptide (PTHrP) and its cognate receptor (PTHrP‐R), and release immunoreactive PTHrP in the extracellular medium; it was also found that PTHrP, in turn, exerts a role on the proliferative and invasive behavior in vitro of the same cell line. On the other hand, evidence has been produced that adhesion of 8701‐BC cells onto different collagen substrates influences in various ways a number of phenotypic expressions, such as cell growth, motility, invasion of reconstituted basement membrane and production of lytic enzymes of the extracellular matrix (ECM). In light of these previous data, we have examined whether substrates of either reconstituted basement membrane or representative collagen components of the breast tumor stroma (type I, V and OF/LB) might (i) regulate the PTHrP promoter usage and mRNA splicing patterns, (ii) modulate quantitatively the extracellular release of immunoreactive PTHrP (iPTHrP), and (iii) affect the expression of PTHrP‐R . The results obtained give evidence that (i) 8701‐BC cells are able to utilize different start sites and mRNA splicing patterns for PTHrP transcription; (ii) ‘structural’ components of the stroma, such as collagens, are by themselves capable of controlling both the expression pattern of the PTHrP gene and the extent of extracellular release of iPTHrP, and (iii) PTHrP‐R expression can be up‐ or down‐regulated in response to the ECM substrate present. These data demonstrate that PTHrP and PTHrP‐R expression by 8701‐BC neoplastic cells can be modulated by ECM molecules, indirectly supporting the active participation of stromal collagen composition in the regulation of PTHrP‐controlled circuits which may play a role in carcinogenesis.