Chemokines are key

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Chemokines are key

How chemokines exert their decis­ive role in inflam­ma­tion and can­cer was recently elu­cid­ated by a research team led by ISAR Chair­man Martin Lohse.

An inter­na­tional team of research­ers led by ISAR Chair­man Martin Lohse used advanced micro­scopy tech­no­lo­gies to invest­ig­ate how a spe­cific chemokine receptor (CXCR4) behaves on the cell sur­face. The team reports form­a­tion of receptor dimers, which appears to be par­tic­u­larly prom­in­ent on can­cer cells that have a lot of these recept­ors. Com­pounds that block this dimer­iz­a­tion might become future drugs.

Back­ground: Chemokines are import­ant mes­sen­gers in inflam­ma­tion, cell migra­tion and can­cer. They cause dif­fer­ent cells to set out on their jour­ney. In the devel­op­ment of an organ­ism, they ensure that cells find their place. In inflam­ma­tion, they attract immune cells to the site. And they also seem to play a role in the meta­stasis of can­cer cells. They are inter­est­ing for stem cell research­ers because with their help stem cells could be brought to where they are needed to regen­er­ate dis­eased tissue.

Study details: There are many dif­fer­ent chemokines and also many recept­ors that recog­nize them. Martin Lohse’s team has found out how such chemokine recept­ors inter­act. Together with research­ers from the Neth­er­lands, Great Bri­tain and Bel­gium, the sci­ent­ists invest­ig­ated how a spe­cific chemokine receptor, called CXCR4, behaves on the cell sur­face. In their pub­lic­a­tion in the renowned journal Pro­ceed­ings of the National Academy of Sci­ences USA, they report that the more recept­ors there are on a cell, the more do the recept­ors form dimers. On can­cer cells, which often carry very many of these recept­ors, dimer form­a­tion there­fore pre­dom­in­ates. Cer­tain sub­stances that block the CXCR4 recept­ors also inhibit pair form­a­tion. Such sub­stances might be of par­tic­u­lar use for future can­cer therapies.

Işb­i­lir A, Möller J, Arimont M, Bob­kov V, Per­piñá-Viciano C, Hoff­mann C, Inoue A, Heuk­ers R, de Graaf C, Smit MJ, Anni­bale P, Lohse MJ (2020) Advanced fluor­es­cence micro­scopy reveals dis­rup­tion of dynamic CXCR4 dimer­iz­a­tion by sub­pocket-spe­cific inverse agon­ists. Proc Natl Acad Sci U S A 117: 29144–29154.
doi: 10.1073/pnas.2013319117.