title: Tumor cell cross talk with tumor-associated leukocytes leads to induction of tumor exosomal fibronectin and promotes tumor progression.
abstract: Exosomes participate in intercellular communication, but most data published are based on exosomes released from in vitro cultured cells that do not communicate with neighboring cells located in the same microenvironment as the exosomal-producing cells in vivo. In this study, our data show that co-culture of leukocytes isolated from breast tumor tissue leads to uptake of fibronectin (FN) on or in the tumor exosomes (Exo(fib+)). The induction of FN and exosomal uptake is tumor tissue derived and leukocyte specific, because leukocytes isolated from the peripheral blood of naïve mice failed to induce FN uptake by tumor exosomes. Furthermore, depletion of both CD25(+) cells and Gr-1(+) cells from tumor-associated leukocytes causes a reduction of Exo(fib+), suggesting that tumor-associated CD25(+) cells and Gr-1(+) cells participate in FN production and uptake by tumor exosomes, resulting in Exo(fib+). As a result of tumor cells absorbing Exo(fib+), two major events are induced: focal adhesion kinase/Src-dependent signaling pathways are activated, and the production of proinflammatory cytokines and metalloproteinase 9 is enhanced in response to absorbing exosomes. This, in turn, enhances tumor cell invasion in vitro and in vivo. Collectively, our findings provide evidence that exosomes released from freshly excised tumor tissue cells that have communicated/interacted with immune cells gain new immune evasion capacity.
authors: Department of Research & Development, Robley Rex Medical Center, Louisville, Kentucky, USA.
authors: ZhongBin
authors: Z
authors: Deng
authors: Ziqiang
authors: Z
authors: Cheng
authors: Xiaoyu
authors: X
authors: Xiang
authors: Jun
authors: J
authors: Yan
authors: Xiaoying
authors: X
authors: Zhuang
authors: Cunren
authors: C
authors: Liu
authors: Hong
authors: H
authors: Jiang
authors: Songwen
authors: S
authors: Ju
authors: Lifeng
authors: L
authors: Zhang
authors: William
authors: W
authors: Grizzle
authors: James
authors: J
authors: Mobley
authors: Jesse
authors: J
authors: Roman
authors: Donald
authors: D
authors: Miller
authors: Huang-Ge
authors: HG
authors: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000503:physiopathology*; D018450:Disease Progression; D055354:Exosomes / Q000502:physiology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D007962:Leukocytes / Q000502:physiology*; D008175:Lung Neoplasms / Q000503:physiopathology / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D005353:Fibronectins