Extracellular matrix regulation of PTHrP and PTH/PTHrP receptor in a human breast cancer cell line

Abstract

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 downregulated 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.z 1999 Federation of European Biochemical Societies.

Characterisation of ligand binding to the parathyroid hormone/parathyroid hormone‐related peptide receptor in MCF7 breast cancer cells and SaOS‐2 osteosarcoma cells

“…18 In contrast, when ROS 17/2.8 cells were treated with DEX for 6 and 24 h, the specific binding of 125 I-PTHrP-1-36 was increased, but when the same cells were treated with progesterone the effect of DEX on PTH/PTHrP-R expression was diminished. 19 There are some comparable data from KPL-3C and MCF7 cell lines on the effect of phorbol ester, steroid hormones, anti-estrogens and extracellular matrix (ECM) [26][27][28][29] but no reports on the effects of EGF, 1,25DHCC and DEX on PTH/PTHrP-R protein or gene expression in breast cancer cells. Nevertheless the data here suggest an additional mechanism by which the use of vitamin D analogues may act to suppress the proliferation of breast cancer cells.…”

Allele-specific patterns of the mouse parathyroid hormone-related protein: influences on cell adhesion and migration

“…The similar adhesion capability of NCI-H520 cells on two different matrices indicates that adhesion of these cells is mediated by multiple types of integrins. Reported interactions between PTHrP and extracellular matrix include regulation of collagen synthesis by PTHrP in chondrocytes, and extracellular matrix modulation of PTHrP promoter usage, mRNA splicing patterns, and extent of extracellular release (Luparello et al, 1999;Goomer et al, 2000). A recent study showed that the increased production of PTHrP in stable transfectants of a human colon cancer cell line significantly enhanced cell adhesion to type I collagen, raising the possibility that PTHrP is involved in colon tumor invasion and metastasis (Ye et al, 2001).…”

Midregion PTHrP regulates Rip1 and caspase expression in MDA-MB231 breast cancer cells

“…Breast cancer was one of the original tumors from which PTHrP was purified and sequenced [17], and it is now known that it is a key factor controlling bone homing and resorption by metastasizing breast cells [2]. Some of us have reported that PTHrP expression by neoplastic breast cells ''in vitro'' is drastically modulated by modifications of the culture microenvironment [18,19]; in addition, data have been produced demonstrating that different PTHrP domains are also biologically-active on breast tumour cells in culture [20][21][22]. In particular, PTHrP (38-94)-amide, administered at 1 nM concentration was found able to restrain growth and invasion as well as to cause striking toxicity and accelerate death of a panel of breast cancer cell lines, the most responsive being MDA-MB231.…”