Protein and production process and use thereof

#The present invention relates to a novel soluble protein having an activity of inhibiting angiogenesis and/or an activity of inhibiting bone resorption by osteoclast activation, a process for producing the same, and a novel diagnostic agent and therapeutic agent using the protein.

#The “angiogenesis” refers to formation of new blood vessels in the body. For angiogenesis, there are a promoter and an inhibitor, and their balance regulates angiogenesis. It is said that the total length of the blood vascular system in an adult reaches 10 km, the surface area of vascular endothelial cells is 7000 m2, and the weight thereof is 1 kg, and the blood vascular system is considered as the largest organ in human, which is distributed in every site in the living body. Angiogenesis occurs vigorously in an embryonic stage or in a process of growth, but in an adult body, angiogenesis is not observed except for special cases such as ovulation and wound healing. The blood vascular system is essential for maintaining the life, and the angiogenesis is a normal reaction in the living body.

#On the other hand, abnormal angiogenesis other than that described above causes various diseases. The typical example is cancer angiogenesis. Angiogenesis in cancer tissues brings about a significant increase in cancer as well as hyper-metastasis. Accordingly, if angiogenesis through which nutrients are supplied into cancer cells were inhibited, the cancer could be kept in tumor dormancy. Folkman et al. , who proposed tumor dormancy, have identified angiogenesis inhibitors produced by cancer cells and named them angiostatin and endostatin (Non-patent document 1: O'Reilly et al., Cell, USA, Vol. 79, No. 2, pp. 315-328, Oct. 21, 1994, Non-patent document 2: O'Reilly et al., Cell, USA, Vol 88, No. 2, pp. 277-285, Jan. 24, 1997). It was revealed that these angiogenesis inhibitors almost completely regress cancei-s in mice, and thereafter angiogenesis has been extensively studied. At present, many pharmaceutical companies are struggling to develop angiogenesis inhibitors and are conducting clinical tests on cancer, but do not arrive at success in overcoming cancer, and there is a need for novel angiogenesis inhibitors

#<Soluble Polypeptides S-ChM1L and MS-ChM1L or Nucleic Acid Molecules Encoding them>

#The present invention relates to a novel soluble polypeptide having an activity of inhibiting angiogenesis and/or an activity of inhibiting bone resorption by osteoclasts.

#The phenomenon “angiogenesis” wherein capillary blood vessels are newly formed is known to occur through the following steps: (1) digestion with matrix metalloprotease (MMP) etc. in an extracellular matrix in a blood vessel basement membrane and therearound, (2) migration of vascular endothelial cells, (3) growth of the vascular endothelial cells, and (4) capillary tube formation. The inhibition of angiogenesis referred to in the present invention means an activity of substantially inhibiting angiogenesis by participation in any of the above steps.