For most cancers, the cause of patient death is either local
invasion into critical areas or metastasis - dissemination of tumor cells from
the primary tumor to many parts of the body followed by formation of new tumors
at those distant sites. By understanding
the mechanisms by which tumor cells invade and metastasize, we will have better
chances of developing appropriate therapies.
Tumor cell motility and the orientation of tumor cells by chemotaxis
make important contributions to invasion and metastasis.
Three types of
cancer are being studied. Glioblastoma
and head and neck cancer invade locally into critical areas and the primary
tumors are not fully removable by surgery.
Breast cancer, although the primary tumor can be fully removed,
metastasizes to distant sites, and the resulting metastases can lead to poor
prognosis. Tissue culture studies of invasion
and signaling of these cancers are combined with in vivo analysis in mice.
Two types of in vivo
approaches being used for studying invasion and metastasis: 1) injection of
tumor cells into the orthotopic site (brain, floor of mouth, or mammary fat pad
for glioma, head and neck cancer, and breast cancer respectively), and 2)
formation of tumors in transgenic mice using oncogenes. The injection assays allow the rapid
molecular manipulation of cell lines to identify important signaling pathways
that contribute to metastasis. The
transgenic mouse system provides a more clinically relevant model in which
tumors develop from the appropriate tissue directly.
The lab has also studied Dictyostelium discoideum and Saccharomyces cerevisiae. Dictyostelium and Saccharomyces provide a molecular/genetic dissection of chemotaxis. Both utilize G protein-coupled signal transduction pathways to mediate orientation responses. The movies sections demonstrate examples of these valuable model systems for studies of chemotaxis and directed cell responses.
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Zhou ZN,
Sharma VP, Beaty BT, Roh-Johnson M, Peterson EA, Van Rooijen N, Kenny PA, Wiley
HS, Condeelis JS, Segall JE. Autocrine HBEGF expression promotes breast cancer
intravasation, metastasis and macrophage-independent invasion in vivo. Oncogene.
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Coniglio SJ,
Segall JE. Review: molecular mechanism of microglia stimulated glioblastoma
invasion. Matrix Biol. 2013 32(7-8):372-80.
Ishihara D,
Dovas A, Hernandez L, Pozzuto M, Wyckoff J, Segall JE, Condeelis JS, Bresnick AR, Cox D. Wiskott-Aldrich
syndrome protein regulates leukocyte-dependent breast cancer metastasis. Cell
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Entenberg D,
Kedrin D, Wyckoff J, Sahai E, Condeelis J, Segall JE. Imaging tumor cell
movement in vivo. Curr Protoc Cell Biol. 2013 Chapter 19:Unit19.7.
Friedl P,
Locker J, Sahai E, Segall JE. Classifying collective cancer cell invasion. Nat
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