Development Cell: Breast cancer cells use exocystic "dialogue" to hold normal cells hostage.

Introduction: Breast cancer is the second leading cause of cancer-related death among women and the most common type of invasive cancer in women.
, breast cancer mortality has declined significantly over the past two decades, largely due to early detection and improved treatment methods.
, however, it's not clear exactly how breast cancer cells attack the normal cells around them, according to a recent study published in Developmental Cells.
extracellular follicles are secreted from the cells to the outside of the cells and usually act as intercellular communication.
especially for tumors, the secretion of extracellular vesicles not only enables tumor cells to escape immune capture, but also has the effect of improving the micro-environment of metastasis of distant tumors.
, extracellular cysts have received more and more scholars' attention.
, according to a study by the Wistar Institute, the messages sent by breast cancer cells when they are oxygen-deprived can cause cancer in the surrounding normal skin cells.
this information is packaged into a particle called an extracellular vesicle (EVs) and the shape and position of the mitochondrials are reprogrammed within the normal cells of the receptor, eventually removing tissue morphology.
the findings were published in the journal Developmental Cell.
"It is well known that cancer cells have been "talking" to neighboring normal cells, which is important for promoting cancer progress," said Dr. Dario C. Altieri, director of the Cancer Center at the Vista Institute and a professor at Robert and Penny Fox and lead author of the study.
how cancer progresses and what signals are transferred from one cell to another remains an open question.
understanding of this process may provide us with important clues as to how tumors hijack nearby normal cells to promote disease recurrence.
in their study, Altieri's team cultured breast cancer cells in a low-oxygen environment to simulate hypoxia, a hallmark of the micro-environment around most solid tumors, and studied the extracellular follicles (EVs) released by these cells.
EVs are tiny structures that are encased in a double-film layer and released by most cells, transmitting different molecules and information to other cells.
, the follicles are an important means of communication between cells.
the study, the researchers focused on small EVs of 30 to 150 nanometers.
to analyze the effects of small extracellular follicles (sEVs) produced by cancer cells on neighboring normal cells, the researchers cultured sEVs released by cells in a hypoxia-deprived state in normal mammary epithal cells.
they observed an increase in the ability of normal subject cells to migrate in cultured fluids, which in turn was associated with the redo distribution of mitochondrials to extracellular periters.
this is consistent with the role of mitochondrials previously described in Altieri's lab in supporting cell movement.
the hypoxic sEVs (sEVHYP) of breast cancer sources stimulate normal mammary epithelial cell movement Altieri and his colleagues further confirmed that the integrator-connected kinase (ILK) is the main signal transducting component packaged in sEVs, responsible for mitochondrial changes and increased migration of the subject cells.
, the activation of the ILK signal profoundly affects the formation of normal tissue morphology.
Normal breast development using a 3D cell model, the team found that using a normal 3-D model of breast development, the team produced sEVs from hypoxia-deprived cancer cells, which led to fractures in normal breast structures and a variety of characteristics that induced tumor metastasis, including morphological changes, cell proliferation out of control, decreased cell death, and the emergence of epithyl-interstitine mass transformation (EMT) markers, a process that gave cancer cells the ability to move and migrate from the primary site.
"Our findings suggest that breast cancer cells may use sEVs to trigger local and distant disease progression," said Dr. Irene Bertolini, a postdoctoral researcher at Altieri Lab and lead author of the study.
based on these observations, we believe that ILK or mitochondrial weight-programmed therapeutic targets may provide new strategies to disrupt these pre-tumor changes in the micro-environment.
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