Ge. Ayala et al., In vitro dorsal root ganglia and human prostate cell line interaction: Redefining perineural invasion in prostate cancer, PROSTATE, 49(3), 2001, pp. 213-223
BACKGROUND. Little is understood regarding mechanisms of perineural invasio
n in Prostate cancer progression. We present a novel model system and data
that indicate perineural invasion is an active, specific, and reciprocal in
teraction between nerves and prostate cancer cells.
METHODS. Mouse dorsal root ganglia (DRG) and human prostate cancer cells (D
u-145, LNCaP, PC3) and stromal cells (HTS-40F) were co-cultured in Matrigel
matrix. Control cultures consisted of prostate cancer and stromal cells on
ly and DRG only. Neurite outgrowth, cell colony growth, neurite-colony cont
act, and retrograde extension were quantitated with dark phase microscopy a
nd image analysis (Optimas 6.1).
RESULTS. Directional outgrowth of neurites was observed projecting into DU-
145 colonies within 24 hr of co-culture. Cultures with the greatest number
of DU-145 cells recruited significantly more neurites and established conta
ct earlier, indicating this process was cell-seeding density dependent. Onc
e neurite/DU-145 cell contact was established neurite growth diminished, su
ggesting an active neurite recruitment by DU-145 cells. Subsequent to neuri
te contact, DU-145 cells migrated along neurites in a retrograde fashion in
to the nerve/ganglion of origin (retrograde extension) establishing perineu
ral invasion. In addition to perineural invasion, DU-145 colony growth was
elevated in DRG co-cultures relative to DU-145-only control cell cultures.
Similarly, the degree of neurite outgrowth was elevated in DRG-cell cocultu
res relative to DRG-only control cultures. The same observations were made
with LNCaP and PC3 cells, but interactions between stromal cells and nerves
were not found.
CONCLUSION. This study shows the utility of the prostate cancer/DRG in vitr
o system to study specific mechanism of prostate cancer cell-nerve interact
ion. Morever, these data suggest that perineural invasion mechanisms involv
e active and reciprocal interactions between carcinoma cells and adjacent n
erve/ganglions in prostate cancer progression. (C) 2001 Wiley-Liss, Inc.