Instructor, Department of Anatomy & Structural Biology
A fundamental issue in cancer research is metastatic disease, which is the predominant cause of death in cancer patients. Our research focuses on the pro-invasive tumor microenvironment in breast cancer and how this leads to dissemination and metastasis. By direct observation with multiphoton imaging of live human breast tumors grown in mice, we have shown that dissemination involves active motility of the tumor cells in multicellular streams towards and into blood vessels. We have also found that both autocrine signaling in the tumor cells and paracrine interactions with the infiltrating immune cells in the tumor microenvironment promote these behaviors. Selective profiling of the in vivo migratory human breast tumor cells revealed a gene expression pattern, or “invasion signature”, which resembles embryonic stem cells and is prognostic of metastasis in breast cancer patients. Finally, these migratory tumor cells are growth arrested, and indeed we recently showed that tumor growth and invasion are uncoupled and oppositely regulated, with the non-receptor kinase Arg/Abl2 acting as a switch between the “go” or “grow” states of the tumor cells.
Currently, we are focusing in more detail on these fundamental mechanisms of breast cancer metastasis: How exactly do these autocrine and paracrine signaling loops give an invasive advantage to the tumor cells? How is tumor cell heterogeneity and plasticity regulated inside the primary tumor? Can we visualize by multiphoton microscopy in live tumors how specific gene networks influence these invasive and metastatic behaviors in the tumor cells in real-time? High-resolution analysis of these pathways is needed separately for each step of cancer progression in order to have a complete understanding of metastasis. This is especially important in cases when the same protein can have a promoting function at one metastatic step, but a suppressor function at another step, indicating that decisions on choosing an appropriate therapeutic target can be a lot more complicated than initially thought. Ultimately, it is my hope that dissecting the mechanisms of invasion and dissemination of tumor cells in vivo will lead to novel insights and improved rationale for prognostic and therapeutic target design in breast cancer.
(*: equal contribution author; #: corresponding author)
A Dovas, A Patsialou, AS Harney, J Condeelis and D Cox. Imaging interactions between macrophages and tumor cells that are involved in metastasis in vivo and in vitro. Journal of Microscopy. 2012. [Epub ahead of print: doi: 10.1111/j.1365-2818.2012.03667.x]
E Roussos, J Condeelis# and A Patsialou#. Chemotaxis in Cancer. Nat Rev Cancer. 2011. 11:573-587.
D Wilsker, A Patsialou, PB Dallas, and E Moran. ARID proteins: A diverse family of DNA binding proteins implicated in the control of cell growth, differentiation, and development. Cell Growth & Differentiation. 2002. 13:95-106.
A Patsialou#, Y Wang, J Lin, K Whitney, S Goswami, PA Kenny and J Condeelis. Selective gene expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients. Breast Cancer Res. 2012. 14(5): R139. - Highlighted in Editorial Comment Article: Max S Wicha “Migratory gene expression signature predicts poor patient outcome: Are cancer stem cells to blame?” Breast Cancer Res. 2012. 14(6):114.
V Sharma, B Beaty, A Patsialou H Liu, M Clarke, D Cox, J Condeelis and R Eddy. Reconstitution of in vivo macrophage-tumor cell pairing and streaming motility on one-dimensional micro-patterned substrates. IntraVital. 2012.[dx.doi.org/10.4161/intv.22054]
A Patsialou*, H Gil-Henn*, S Warren, Y Wang, J Condeelis and A Koleske. Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene. 2012. [Epub ahead of print: doi: 10.1038/onc.2012.284]
H Liu*, MR Patel*, JA Prescher*, A Patsialou, S Goswami, D Qian, J Lin, S Wen, YF Chang, M Bachmann, Y Shimono, P Dalerba, M Adorno, N Lobo, FM Dirbas, J Bueno, J Condeelis, CH Contag, SS Gambhir and MF Clarke. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. PNAS. 2010. 07(42): 18115-20.
A Patsialou#, J Wyckoff, Y Wang, S Goswami, ER Stanley and J Condeelis. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony stimulating factor-1 receptor. Cancer Res. 2009. 69(24): 9498-506.
H Pang, R Flinn, A Patsialou, J Wyckoff, E Roussos, H Wu, S Goswami, J Condeelis, J Segall and JM Backer. Differential enhancement of breast cancer cell motility and metastasis by helical and kinase domain mutations of class IA PI3K. Cancer Res. 2009. 69(23): 8868-76.
S Goswami , U Philippar, D Sun, A Patsialou, J Avraham, W Wang, F Di Modugno, P Nistico, FB Gertler, and J Condeelis. Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo. Clin Exp Metastasis. 2009.26:153-9.
NG Nagl Jr, X Wang, A Patsialou, M Van Scoy and E Moran. Distinct Mammalian SWI/SNF chromatin remodeling complexes with opposing roles in cell cycle control. EMBO J. 2007. 26(3): 752-63.
A Patsialou, D Wilsker, and E Moran. DNA binding properties of ARID family proteins. Nucleic Acids Res. 2005. 33(1): 66-80.
NG Nagl Jr, A Patsialou, DS Haines, PB Dallas, GR Beck Jr, and E Moran. The p270 (ARID1A/SMARCF1) subunit of mammalian SWI/SNF-related complexes is essential for normal cell cycle arrest. Cancer Res. 2005. 65(20): 9236-9244.
D Wilsker, A Patsialou, SD Zumbrun, S Kim, Y Chen, PB Dallasand E Moran. The DNA-binding properties of the ARID-containing subunits of yeast and mammalian SWI/SNF complexes. Nucleic Acids Res. 2004. 32(4): 1345-1353.
J Garriga, AL Jayaraman, A Limon, G Jayadeva, E Sotillo, M Truongcao, A Patsialou, BE Wadzinski, and X Grana. A dynamic equilibrium between CDKs and PP2A modulates phosphorylation of pRB, p107 and p130. Cell Cycle. 2004. 3(10): 1320-30.
More Information About Dr. Antonia Patsialou
Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.
Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 208
Bronx, NY 10461