TY - JOUR
T1 - Probing the invasiveness of prostate cancer cells in a 3D microfabricated landscape
AU - Liu, Liyu
AU - Sun, Bo
AU - Pedersen, Jonas Nyvold
AU - Yong, Koh-Meng Aw
AU - Getzenberg, Robert H.
AU - Stone, Howard A.
AU - Austin, Robert H.
PY - 2011
Y1 - 2011
N2 - The metastatic invasion of cancer cells from primary tumors to
distant ecological niches, rather than the primary tumors, is the
cause of much cancer mortality [Zhang QB, et al. (2010) Int J Cancer
126:2534–2541; Chambers AF, Goss PE (2008) Breast Cancer Res
10:114]. Metastasis is a three-dimensional invasion process where
cells spread from their site of origin and colonize distant microenvironmental
niches. It is critical to be able to assess quantitatively
the metastatic potential of cancer cells [Harma V, et al. (2010) PLoS
ONE 5:e10431]. We have constructed a microfabricated chip with a
three-dimensional topology consisting of lowlands and isolated
square highlands (Tepuis), which stand hundreds of microns above
the lowlands, in order to assess cancer cell metastatic potential as
they invade the highlands. As a test case, the invasive ascents of
the Tepui by highly metastatic PC-3 and noninvasive LNCaP prostate
cancer cells were used. The vertical ascent by prostate cancer
cells from the lowlands to the tops of the Tepui was imaged using
confocal microscopy and used as a measure of the relative invasiveness.
The less-metastatic cells (LNCaP) never populated all available
tops, leaving about 15% of them unoccupied, whereas the more
metastatic PC-3 cells occupied all available Tepuis. We argue that
this distinct difference in invasiveness is due to contact inhibition.
AB - The metastatic invasion of cancer cells from primary tumors to
distant ecological niches, rather than the primary tumors, is the
cause of much cancer mortality [Zhang QB, et al. (2010) Int J Cancer
126:2534–2541; Chambers AF, Goss PE (2008) Breast Cancer Res
10:114]. Metastasis is a three-dimensional invasion process where
cells spread from their site of origin and colonize distant microenvironmental
niches. It is critical to be able to assess quantitatively
the metastatic potential of cancer cells [Harma V, et al. (2010) PLoS
ONE 5:e10431]. We have constructed a microfabricated chip with a
three-dimensional topology consisting of lowlands and isolated
square highlands (Tepuis), which stand hundreds of microns above
the lowlands, in order to assess cancer cell metastatic potential as
they invade the highlands. As a test case, the invasive ascents of
the Tepui by highly metastatic PC-3 and noninvasive LNCaP prostate
cancer cells were used. The vertical ascent by prostate cancer
cells from the lowlands to the tops of the Tepui was imaged using
confocal microscopy and used as a measure of the relative invasiveness.
The less-metastatic cells (LNCaP) never populated all available
tops, leaving about 15% of them unoccupied, whereas the more
metastatic PC-3 cells occupied all available Tepuis. We argue that
this distinct difference in invasiveness is due to contact inhibition.
U2 - 10.1073/pnas.1102808108
DO - 10.1073/pnas.1102808108
M3 - Journal article
C2 - 21474778
SN - 0027-8424
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
ER -
