The Alexander Laboratory
Faculty > Caroline M. Alexander
Caroline M. Alexander
Associate Professor, Oncology
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Organ System/Disease Focus:Cancer Stem Cells
Aligned Research Focus: Mammary stem cells, mouse mammary tumor models, Wnt signaling, Syndecan-1
Research Description
We are studying aspects of mammary gland biology and neoplasia using transgenic mouse models. Particularly, we have found that Wnt signaling dysregulates mammary stem cells, and that this precedes the formation of differentiated, bilineal tumors. Wnt signaling is highly oncogenic to mammalian epithelia, and indeed comprises one of the main sources of human tumor initiation identified to date. Our hypothesis is that the transforming potential of Wnt signaling is unique to stem/progenitor cells. Our work aims to elucidate how and when adult somatic stem cells can be recruited as tumor precursor cells. Current projects include:
- The discovery of the molecular and cellular mechanism that underlies the tumor resistance phenotype illustrated by mice with a mutation in the heparan sulfate proteoglycan, syndecan-1 (Sdc1) (McDermott et al 2006).
- Modeling of stem cell-based breast cancer.
- The activation of stromal cells and their recruitment to tumor development during Wnt-induced tumorigenesis.
- The analysis of adult stem cell responses during tumor initiation.
- Determination of how Wnt signaling supports normal mammary stem cell function.
- An investigation of cell-cell interactions in mammary gland, using micro channel cultures to identify endogenous growth promoting and inhibiting substances secreted by minor sub-populations.
Selected References
N.M. Badders, S. Goel, R.J. Clark, K.S. Klos, S. Kim, A. Bafico, C. Lindvall, B.O. Williams and C.M. Alexander. The Wnt Receptor, Lrp5, is Expressed by Mouse Mammary Stem Cells and is Required to Maintain the Basal Lineage. PLOS One epub Aug 12th 09
M. Mastroianni, Y-C. Kim, A. Esch and C. M. Alexander. Wnt Signaling can Substitute for Estrogen to Induce Division of ERa-positive Cells in a Mouse Mammary Tumor Model. Cancer Lett epub Aug 8th 09
Y-C Kim, R.J. Clark, F. J. Pelegri and C. M. Alexander. Wnt4 is not sufficient to induce lobuloalveolar mammary development. BMC Dev. Biol. in press
Y-C Kim, R.J. Clark, E.A. Ranheim and C.M. Alexander. Wnt1 expression induces short- and long-range cell recruitments that modify mammary tumor development, and are not induced by a cell-autonomous b-catenin effector. Cancer Res., 68: 10145-10153, 2008.
C.M. Alexander. Base Behavior Behind Budding Breasts: Integrins and Mammary Stem Cell Activity. Invited perspective article, Cell Stem Cell, 3: 5-6, 2008.