Circulating Microvesicles from Pancreatic Cancer Accelerate the Migration and Proliferation of PANC‑1 Cells

Circulating microvesicles
are able to mediate long-distance cell–cell
communications. It is essential to understand how microvesicles from
pancreatic cancer act on other cells in the body. In this work, serum-derived
microvesicles were isolated from 10 patients with locally advanced
pancreatic cancer and healthy controls. Using Cell Transwell and WST-1
reagents, we found that microvesicles from pancreatic cancer accelerated
migration and proliferation of PANC-1 cells. Meanwhile, the proliferation
of these cancer-microvesicle-treated cells (CMTCs) was affected less
by 10 μM of gemcitabine relative to healthy microvesicle-treated
cells (HMTCs). Next, we optimized the filter-aided sample preparation
method to increase the recovery of protein samples and then applied
it to the quantification of the proteome of CMTCs and HMTCs. The peptides
were labeled and analyzed by liquid chromatography–tandem mass
spectrometry. In total, 4102 proteins were identified, where 35 proteins
were up-regulated with 27 down-regulated in CMTCs. We verified the
quantitative results of three key proteins CD44, PPP2R1A, and TP53
by Western blot. The Ingenuity Pathway Analysis revealed pathways
that cancer microvesicles might participate in to promote cell migration
and proliferation. These findings may provide novel clues of treatment
for tumorigenesis and metastasis.