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Inhibition of tumor cell proliferation and motility by fibroblasts is both
contact and soluble factor dependent
#MMPMID25404301
Alkasalias T
; Flaberg E
; Kashuba V
; Alexeyenko A
; Pavlova T
; Savchenko A
; Szekely L
; Klein G
; Guven H
Proc Natl Acad Sci U S A
2014[Dec]; 111
(48
): 17188-93
PMID25404301
show ga
Normal human and murine fibroblasts can inhibit proliferation of tumor cells when
cocultured in vitro. The inhibitory capacity varies depending on the donor and
the site of origin of the fibroblast. We showed previously that effective
inhibition requires formation of a morphologically intact fibroblast monolayer
before seeding of the tumor cells. Here we show that inhibition is extended to
motility of tumor cells and we dissect the factors responsible for these
inhibitory functions. We find that inhibition is due to two different sets of
molecules: (i) the extracellular matrix (ECM) and other surface proteins of the
fibroblasts, which are responsible for contact-dependent inhibition of tumor cell
proliferation; and (ii) soluble factors secreted by fibroblasts when confronted
with tumor cells (confronted conditioned media, CCM) contribute to inhibition of
tumor cell proliferation and motility. However, conditioned media (CM) obtained
from fibroblasts alone (nonconfronted conditioned media, NCM) did not inhibit
tumor cell proliferation and motility. In addition, quantitative PCR (Q-PCR) data
show up-regulation of proinflammatory genes. Moreover, comparison of CCM and NCM
with an antibody array for 507 different soluble human proteins revealed
differential expression of growth differentiation factor 15, dickkopf-related
protein 1, endothelial-monocyte-activating polypeptide II, ectodysplasin A2,
Galectin-3, chemokine (C-X-C motif) ligand 2, Nidogen1, urokinase, and matrix
metalloproteinase 3.
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