Pharmaceutical compositions and methods useful for modulating angiogenesis and inhibiting metastasis and tumor fibrosis

A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a nucleic acid construct being capable of expressing a polypeptide having lysyl-oxidase activity to thereby modulate angiogenesis within the mammalian tissue.

A method of identifying molecules capable of modulating angiogenesis, the method comprising:

• (a) isolating molecules which exhibit specific reactivity with at least one type of lysyl-oxidase;
• and
• (b) testing said molecules within mammalian tissue so as to determine the angiogenesis modulation activity thereof.

A pharmaceutical composition useful for modulating angiogenesis in mammalian tissue, the composition-of matter comprising, as an active ingredient, a molecule capable of modifying a level and/or activity of at least one type of lysyl-oxidase of the mammalian tissue and a pharmaceutically effective carrier.

A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a molecule capable of modifying a tissue level and/or a lysyl-oxidase activity of a polypeptide at least 75% homologous to the polypeptide set forth in SEQ ID NO:

• 2 to thereby modulate angiogenesis in the mammalian tissue.

A method of modulating angiogenesis in a mammalian tissue, the method comprising administering into the mammalian tissue a nucleic acid construct being capable of expressing a polypeptide at least 75% homologous to the polypeptide set forth in SEQ ID NO:

• 2 to thereby modulate angiogenesis within the mammalian tissue.

A method of determining the malignancy of cancerous tissue, the method comprising

• (a) determining a lysyl-oxidase expression level and/or activity of the cancerous tissue;
• and
• (b) comparing said lysyl-oxidase expression level and/or activity with that determined for control tissue to thereby determine the malignancy of the cancerous tissue.

A method of inhibiting metastasis and/or fibrosis in a mammalian tissue, the method comprising administering to the mammalian tissue a molecule capable of downregulating a tissue level and/or activity of at least one type of lysyl-oxidase to thereby inhibit metastasis in the mammalian tissue.

A method of identifying molecules capable of inhibiting metastasis and/or fibrosis, the method comprising:

• (a) screening and identifying molecules which exhibit specific reactivity with at least one type of lysyl-oxidase;
• and
• (b) testing a metastasis and/or fibrosis inhibitory potential of said molecules.

A pharmaceutical composition useful for inhibiting metastasis and/or fibrosis in mammalian tissue, comprising, as an active ingredient, a molecule capable of downregulating a level and/or activity of at least one type of lysyl-oxidase present within the mammalian tissue and a pharmaceutically effective carrier.

A method of inhibiting metastasis and fibrosis in a mammalian tissue, the method comprising administering to the mammalian tissue a molecule capable of downregulating a tissue level and/or a lysyl-oxidase activity of a polypeptide at least 75% homologous to the polypeptide set forth in ID NO:

• 2 or 9, to thereby inhibit metastasis and fibrosis in the mammalian tissue.