Molecular characteristics and functional diversity of CLCA family members

1. In the present brief review, we describe some of the molecular and funct ional characteristics of a novel mammalian family of putative Ca2+-activate d chloride channels (CLCA). 2. So far, two bovine (bCLC1; bCLCA2 (Lu-ECAM-1)), three mouse (mCLCA1; mCL CA2; mCLCA3) and four human (hCLCA1; hCLCA2; hCLCA3; hCLCA4) CLCA family me mbers have been cloned. Each CLCA exhibits a distinct, often overlapping, t issue expression pattern. 3. With the exception of the truncated secreted hCLCA3, all CLCA proteins a re synthesized as an approximately 125 kDa precursor transmembrane glycopro tein that is rapidly cleaved into 90 and 35 kDa subunits. 4. The CLCA proteins expressed on the luminal surface of lung vascular endo thelia (bCLCA2; mCLCA1; hCLCA2) serve as adhesion molecules for lung metast atic cancer cells, mediating vascular arrest and lung colonization. 5. Expression of hCLCA2 in normal mammary epithelium is consistently lost i n human breast cancer and in all tumorigenic breast cancer cell lines. Re-e xpression of hCLCA2 in human breast cancer cells abrogates invasiveness of Matrigel (BD Biosciences-Labware, Bedford, MA, USA) in vitro and tumorigeni city in nude mice, implying that hCLCA2 acts as a tumour suppressor in brea st cancer.