Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer.

1. YKL-40 In a search of new bone proteins, the glycoprotein YKL-40 was identified in 1989 to be secreted in vitro in large amount by the human osteosarcoma cell line MG63. The protein was named YKL-40 based on its three N-terminal aminoacids Tyrosine (Y), Lysine (K) and Leucine (L) and its molecular mass of 40 kDa (Johansen et al. 1992). This protein was later found to be similar to a protein secreted by differentiated smooth muscle cells from swine explants of the thoracic aorta (Millis et al. 1985), to a protein isolated from the whey protein secretions of bovine mammary secretions during the nonlactating period (Rejman et al. 1988), and to a heparin binding protein secreted by human synovial cells (Nyirkos et al. 1990). In the last few years there has been a growing number of publications concerning YKL-40 and the “Story about YKL-40” has probably just started. The protein has several names: “YKL-40” (Johansen et al. 1992), “Human Cartilage glycoprotein-39 (HC gp39)” (Hakala et al. 1993), “Breast regressing protein 39 Kd (brp-39)” (Morrison et al. 1994), “38-kDa heparin-binding glycoprotein (gp38k)” (Shackelton et al. 1995), “Chitinase-3-like-1 (CHI3L1)” (Rehli et al. 1997), “Chondrex” (Harvey et al. 1998), and “40 kDa mammary gland protein (MGP-40)” (Mohanty et al. 2003). Hopefully, there will in the future be consensus of its name. In this thesis the protein is named YKL-40.