Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling.
We have developed animal models of breast cancer that allow the direct examination of the behavior of individual green fluorescent protein-expressing carcinoma cells in live nonmetastatic and metastatic primary tumors in situ. We have combined this model with multiphoton microscopy to image differences in cell behavior within the primary tumor. Differences in cell behavior between nonmetastatic and metastatic cells in culture and within live primary tumors were correlated with results from cDNA microarray analyses to identify potentially important genetic determinants for breast cancer invasion and metastasis. Using multiphoton microscopy, we found five major differences in carcinoma cell behavior between the nonmetastatic and metastatic primary breast tumors involving extracellular matrix, cell motility, and chemotaxis. Behavioral differences were correlated with seven categories of molecules that were differentially expressed and related to these behaviors. We have found that extracellular matrix composition, actin nucleation factors, molecules involved in mechanical stability and survival, and cell polarity and chemotaxis showed large and consistent differences in gene expression. We conclude that aligning cell behavior in vivo with patterns of gene expression can lead to new insights into the microenvironment of carcinoma cells in the primary tumor and the molecular mechanisms behind cell behavior.
Wang
Weigang
W
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Wyckoff
Jeffrey B
JB
Frohlich
Victoria Centonze
VC
Oleynikov
Yuri
Y
Hüttelmaier
Stefan
S
Zavadil
Jiri
J
Cermak
Lukas
L
Bottinger
Erwin P
EP
Singer
Robert H
RH
White
John G
JG
Segall
Jeffrey E
JE
Condeelis
John S
JS
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D020869:Gene Expression Profiling; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D003094:Collagen