There are many ways in which the aging of tissue makes cancer both more likely to occur and more aggressive once it does occur. Here researchers focus in on specific changes in aged skin tissue that make melanoma cancers more likely to become metastatic and spread to other organs. Interestingly, it is an indirect effect on cell signaling that is mediated by increased stiffness of the skin extracellular matrix, an issue in many aging tissues that has many root causes, not just the one noted here. Nonetheless, if metastasis could be shut down, then cancer would become a much more tractable problem, particularly if control of metastasis were to be combined with improved approaches to the early detection of cancer.
Previous research has shown that a protein called HAPLN1 helps maintain the structure of the extracellular matrix, a network of molecules and minerals that provide structural support, to keep the skin supple. As people age, they release less HAPLN1, which causes the skin to stiffen. A new study shows that reduced HAPLN1 indirectly increases ICAM1 levels by causing stiffening, which alters cellular signaling. The increase in ICAM1 contributes to angiogenesis, or the growth of new blood vessels that supply the tumors with nutrients and help them grow. The blood vessels are also leakier, making it easier for tumor cells to escape from the initial tumor site and spread to distant areas of the body.
Treating older mice with melanoma with drugs that block ICAM1, however, prevents these changes, shrinking their tumors and reducing metastasis, researchers demonstrated. The researchers are now studying ICAM1's activities to develop more precise ways of targeting it with drugs, which might lead to new approaches to treating older people with melanoma. The discoveries might also lead to new approaches to treating other age-related cancers. Previous therapies targeting growth factors that contribute to angiogenesis have failed in many tumor types, including melanoma. But ICAM1 provides a promising new target.
Link: https://www.eurekale...eleases/1037180
View the full article at FightAging
