Oral cancer develops in the oral mucosa and has a tendency to invade the bone tissue (jawbone) directly below. When cancer invades the bone through the periosteum that surrounds the bone, the patient's prognosis significantly worsens.

　The research group focused on the fact that bone invasion involves the periosteum, which is different from bone metastasis, in which cancer invades bone tissue via the bloodstream, and attempted to clarify the function of the periosteum in cancer bone invasion. After detailed analysis of samples from oral cancer patients, they found that the thickness of the periosteum increased 3-4 times in areas where oral cancer was close to the bone.

　We developed a mouse model of oral cancer bone invasion and further analyzed it, and found that periosteal cells increased in bone tissue close to cancer cells, and that expression of the protease inhibitor Timp1 was significantly increased. In mice lacking the Timp1 gene, periosteal thickening did not occur in response to the proximity of cancer to bone, and cancer bone invasion progressed more markedly than in normal mice, leading to earlier death. This suggests that periosteal thickening acts as a defensive barrier that physically suppresses cancer bone invasion.

　These results revealed a unique phenomenon in which periosteal cells release Timp1 in response to the proximity of cancer, inhibiting proteases, a protein-degrading enzyme, thickening the periosteum (forming a defense wall mainly composed of collagen), and that periosteal thickening physically inhibits cancer invasion of bone. This result is the first in the world to reveal a completely new anti-cancer mechanism possessed by cells other than the immune system, and is expected to contribute to the development of new anti-cancer treatments based on innovative concepts that target non-immune cells.

Paper information:【Nature】The periosteum provides a stromal defense against cancer invasion into the bone