Abstract
BACKGROUND. The mechanism of epithelial to mesenchymal transition (EMT) could be adopted by tumor cells for migration and invasion. We have reported that ARCaPE human prostate cancer cells undergo EMT-like changes during xenograft growth in athymic mice. METHODS. In this report, we assessed the extent of EMT by tracking changes in cloned ARCaPE cells expressing red fluorescence protein during successive orthotopic prostate tumor formation. Cancer cells with stromal-like morphology were isolated and examined for EMT-like changes. RESULTS. EMT-like morphologic and expression changes were detected after one round of in vivo tumor formation. Importantly, when recovered tumor cells were used in second round xenograft tumor formation, a large fraction of ARCaPE cells showed drastic EMT-like changes, with markedly enlarged cell size and divergent cell shapes similar to those of mesenchymal stromal cells. The morphologic change was accompanied by increased growth and metastasis, as tumor incidence increased while red fluorescent tumor cells could be detected from circulating blood, bone marrow, peritoneal ascites, and lung of the tumor-bearing mice. Recovered clones from these samples had lost epithelial markers but many showed activated stromal marker vimentin expression. The EMT appeared permanent since the newly acquired morphology was sustained after continuous passages. CONCLUSIONS. Results from this study demonstrate that through interaction with the host tumor microenvironment, cancer cells acquire cellular plasticity. During xenograft tumor formation and metastasis, a single clone of cancer cells could yield a heterogeneous population, with a substantial number of tumor cells adopting mesenchymal stroma-like phenotypes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 518-528 |
| Number of pages | 11 |
| Journal | Prostate |
| Volume | 70 |
| Issue number | 5 |
| DOIs | |
| State | Published - Apr 1 2010 |
| Externally published | Yes |
Fingerprint
Keywords
- Epithelial to mesenchymal transition
- Orthotopic tumor formation
- Prostate cancer progression and metastasis
- Red fluorescence protein
ASJC Scopus subject areas
- Oncology
- Urology
Cite this
Progressive epithelial to mesenchymal transitions in ARCaPE prostate cancer cells during xenograft tumor formation and metastasis. / He, Hui; Yang, Xiaojian; Davidson, Alec J.; Wu, Daqing; Marshall, Fray F.; Chung, Leland W.K.; Zhau, Haiyen E.; Wang, Ruoxiang.
In: Prostate, Vol. 70, No. 5, 01.04.2010, p. 518-528.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Progressive epithelial to mesenchymal transitions in ARCaPE prostate cancer cells during xenograft tumor formation and metastasis
AU - He, Hui
AU - Yang, Xiaojian
AU - Davidson, Alec J.
AU - Wu, Daqing
AU - Marshall, Fray F.
AU - Chung, Leland W.K.
AU - Zhau, Haiyen E.
AU - Wang, Ruoxiang
PY - 2010/4/1
Y1 - 2010/4/1
N2 - BACKGROUND. The mechanism of epithelial to mesenchymal transition (EMT) could be adopted by tumor cells for migration and invasion. We have reported that ARCaPE human prostate cancer cells undergo EMT-like changes during xenograft growth in athymic mice. METHODS. In this report, we assessed the extent of EMT by tracking changes in cloned ARCaPE cells expressing red fluorescence protein during successive orthotopic prostate tumor formation. Cancer cells with stromal-like morphology were isolated and examined for EMT-like changes. RESULTS. EMT-like morphologic and expression changes were detected after one round of in vivo tumor formation. Importantly, when recovered tumor cells were used in second round xenograft tumor formation, a large fraction of ARCaPE cells showed drastic EMT-like changes, with markedly enlarged cell size and divergent cell shapes similar to those of mesenchymal stromal cells. The morphologic change was accompanied by increased growth and metastasis, as tumor incidence increased while red fluorescent tumor cells could be detected from circulating blood, bone marrow, peritoneal ascites, and lung of the tumor-bearing mice. Recovered clones from these samples had lost epithelial markers but many showed activated stromal marker vimentin expression. The EMT appeared permanent since the newly acquired morphology was sustained after continuous passages. CONCLUSIONS. Results from this study demonstrate that through interaction with the host tumor microenvironment, cancer cells acquire cellular plasticity. During xenograft tumor formation and metastasis, a single clone of cancer cells could yield a heterogeneous population, with a substantial number of tumor cells adopting mesenchymal stroma-like phenotypes.
AB - BACKGROUND. The mechanism of epithelial to mesenchymal transition (EMT) could be adopted by tumor cells for migration and invasion. We have reported that ARCaPE human prostate cancer cells undergo EMT-like changes during xenograft growth in athymic mice. METHODS. In this report, we assessed the extent of EMT by tracking changes in cloned ARCaPE cells expressing red fluorescence protein during successive orthotopic prostate tumor formation. Cancer cells with stromal-like morphology were isolated and examined for EMT-like changes. RESULTS. EMT-like morphologic and expression changes were detected after one round of in vivo tumor formation. Importantly, when recovered tumor cells were used in second round xenograft tumor formation, a large fraction of ARCaPE cells showed drastic EMT-like changes, with markedly enlarged cell size and divergent cell shapes similar to those of mesenchymal stromal cells. The morphologic change was accompanied by increased growth and metastasis, as tumor incidence increased while red fluorescent tumor cells could be detected from circulating blood, bone marrow, peritoneal ascites, and lung of the tumor-bearing mice. Recovered clones from these samples had lost epithelial markers but many showed activated stromal marker vimentin expression. The EMT appeared permanent since the newly acquired morphology was sustained after continuous passages. CONCLUSIONS. Results from this study demonstrate that through interaction with the host tumor microenvironment, cancer cells acquire cellular plasticity. During xenograft tumor formation and metastasis, a single clone of cancer cells could yield a heterogeneous population, with a substantial number of tumor cells adopting mesenchymal stroma-like phenotypes.
KW - Epithelial to mesenchymal transition
KW - Orthotopic tumor formation
KW - Prostate cancer progression and metastasis
KW - Red fluorescence protein
UR - http://www.scopus.com/inward/record.url?scp=77949877839&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949877839&partnerID=8YFLogxK
U2 - 10.1002/pros.21086
DO - 10.1002/pros.21086
M3 - Article
C2 - 19918799
AN - SCOPUS:77949877839
VL - 70
SP - 518
EP - 528
JO - Prostate
JF - Prostate
SN - 0270-4137
IS - 5
ER -