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Multiple Myeloma           
Breast Cancer

Model Systems

rBM culture
rMet model
Humanized bone marrow mouse model

Protocols
rBM culture
rMet model
Cell recovery
DNA/RNA purification
Humanized bone marrow mouse model
RESEARCH INTERESTS

The long-term research objective of the Kirshner lab is to investigate the fundamental question in cancer stem cell biology.  What is the role of microenvironment in maintaining the balance between self-renewal and differentiation of cancer stem cells?  Answering this question will provide information on how to keep the cancer stem cells from initiating tumors and their relapse.



Tumor Microenvironment

Past research has largely focused on the cancer cell as a stand-alone entity, however, more recent studies have emphasized the importance of tissue environment in the development and maintenance of the malignancy.  The term tumor microenvironment thus refers to the cells, extracellular matrix, and any other molecules that surround a tumor cell, found either in direct contact or in proximity of the tumor and capable of influencing the tumor behavior.  A number of studies have shown that tumorigenesis does not proceed without permissive microenvironment.



Cancer Stem Cells

Strong evidence in support of the cancer stem cell theory has been steadily accumulating over the last decade shifting the accepted cancer initiation paradigm from the stochastic model, which proposes that every cell within the tumor is capable of re-growing the malignancy, to the cancer stem cell hypothesis, the idea that only a small sub-population of the tumor cells are capable of initiating and/or maintaining a malignancy.  In addition to tumorigenic potential, cancer stem cells possess characteristics of normal stem cells including proliferative quiescence and self-renewal potential. Upon receiving proliferation signal(s) from the microenvironment, a cancer stem cell switches its program from quiescence to proliferation, initiating tumor growth.



PROJECTS

A number of projects are under way to identify and characterize cancer stem cells, to define their microenvironment, and to evaluate the signaling events responsible for tumor initiation, relapse, and metastatic spread of cancer.
  • Determine the phenotype of the multiple myeloma cancer stem cell;
  • Define the niche within the bone marrow microenvironment capable of supporting self-renewal of the multiple myeloma cancer stem cells;
  • Determine how bone marrow microenvironment regulates differentiation of multiple myeloma cancer stem cells;
  • Dissect the signal transduction pathways guiding breast cancer colonization of bone and other tissues during metastatic spread;
  • Identify new compounds with specificity and selectivity against cancer stem cells.


Our working hypothesis is that cancer stem cells are found in a specialized microenvironment niche which keeps the cells in a non-proliferative state. Altering the conditions in favor of  differentiation and proliferation leads to tumor re-growth.


















Characteristics of normal tissue stem cells and cancer stem cells.






Last modified:  March 8, 2011