Unregistered
03-20-2006, 09:25 AM
This is a technical but comrehensible article.
It helped me understand a bit more what a cancer is - how complex it is - how much is still to know- why cancers are "individual" - and suggests that there is no reason why factors such as diet and environment should not have significant impact as triggers or "feeders".
RB
http://www.cancer.gov/think-tanks-cancer-biology/page3
ABSTRACT
The intrinsic and extrinsic influences that transform a normal epithelial cell into a malignant cell are very complex. Enormous advances have been made over the last several decades in identifying the molecular and genetic changes of cancer cells and the pathogenesis of neoplasia. This has led to the identification of oncogenes and tumor suppressor genes and associated signaling mechanisms by which they modulate growth, survival and proliferation. These studies have generated novel therapeutic reagents such as Tamoxifen, Herceptin and Gleevec.
Stromal influence on epithelia cells begins at fertilization and continues during adulthood, wherein the microenvironment controls normal development and homeostasis. For example, macrophage association with the developing mammary gland is critical during development and CSF-1 or CSF-1R null mice (devoid of macrophage) have defective mammary glands.
Research on tumor-host interactions collectively suggests that (a) tumors are not autonomous masses of cells but function as organs composed of many interdependent cell types that contribute to tumor development and metastasis, and (b) the interactions between the tumors, the extracellular matrix (ECM) and stromal cells is bidirectional and dynamic; stromal cells include fibroblasts, adipocytes, glial cells, smooth muscle cells, and resident and recruited vascular and immune cells.
The tumor microenvironment and the malignant cells themselves constitute the tumor entity that clinicians confront when treating cancer patients. The cell-cell and cell-matrix interactions that influence the behavior of cancer cells are targets with as much potential for the development of effective therapies as the tumor cells themselves. The microenvironment can exert both positive and negative influences on tumor cells. Stromal cells can also impart stimulatory and growth inhibitory effects on tumor cells, e.g., the malignant potential of teratocarcinoma cells can be restrained during embryonic development resulting in cancer-free adult mice. Similarly, attenuation of β1 integrin (laminin receptor), EGFR or MAPK activation in highly aggressive human breast cancer cells results in a reversion of the aggressive phenotype.
The cancer cell is absolutely dependent on the stroma for its proliferation, progression, and metastasis; examples include the role of inflammatory cells (via cytokine and protease secretion) in tumor cell proliferation, angiogenesis, invasion and metastasis; the interaction of host immune cells with the vasculature; the interaction of tumor cells with the angiogenic endothelial cells, and the role of lymphangiogenesis during metastasis to the regional lymph nodes. Stromal cells can also influence organ-specific metastasis as evidenced by the role of stromal-derived cytokines and growth factors (e.g., PTHrP, CXCR4, SDF1, TGF B and RANKL) in breast and prostate cancer and multiple myeloma metastasis to bone. Finally, interaction of bone marrow stromal cells with multiple myeloma cells has been shown to contribute to the development of drug resistance.......................
It helped me understand a bit more what a cancer is - how complex it is - how much is still to know- why cancers are "individual" - and suggests that there is no reason why factors such as diet and environment should not have significant impact as triggers or "feeders".
RB
http://www.cancer.gov/think-tanks-cancer-biology/page3
ABSTRACT
The intrinsic and extrinsic influences that transform a normal epithelial cell into a malignant cell are very complex. Enormous advances have been made over the last several decades in identifying the molecular and genetic changes of cancer cells and the pathogenesis of neoplasia. This has led to the identification of oncogenes and tumor suppressor genes and associated signaling mechanisms by which they modulate growth, survival and proliferation. These studies have generated novel therapeutic reagents such as Tamoxifen, Herceptin and Gleevec.
Stromal influence on epithelia cells begins at fertilization and continues during adulthood, wherein the microenvironment controls normal development and homeostasis. For example, macrophage association with the developing mammary gland is critical during development and CSF-1 or CSF-1R null mice (devoid of macrophage) have defective mammary glands.
Research on tumor-host interactions collectively suggests that (a) tumors are not autonomous masses of cells but function as organs composed of many interdependent cell types that contribute to tumor development and metastasis, and (b) the interactions between the tumors, the extracellular matrix (ECM) and stromal cells is bidirectional and dynamic; stromal cells include fibroblasts, adipocytes, glial cells, smooth muscle cells, and resident and recruited vascular and immune cells.
The tumor microenvironment and the malignant cells themselves constitute the tumor entity that clinicians confront when treating cancer patients. The cell-cell and cell-matrix interactions that influence the behavior of cancer cells are targets with as much potential for the development of effective therapies as the tumor cells themselves. The microenvironment can exert both positive and negative influences on tumor cells. Stromal cells can also impart stimulatory and growth inhibitory effects on tumor cells, e.g., the malignant potential of teratocarcinoma cells can be restrained during embryonic development resulting in cancer-free adult mice. Similarly, attenuation of β1 integrin (laminin receptor), EGFR or MAPK activation in highly aggressive human breast cancer cells results in a reversion of the aggressive phenotype.
The cancer cell is absolutely dependent on the stroma for its proliferation, progression, and metastasis; examples include the role of inflammatory cells (via cytokine and protease secretion) in tumor cell proliferation, angiogenesis, invasion and metastasis; the interaction of host immune cells with the vasculature; the interaction of tumor cells with the angiogenic endothelial cells, and the role of lymphangiogenesis during metastasis to the regional lymph nodes. Stromal cells can also influence organ-specific metastasis as evidenced by the role of stromal-derived cytokines and growth factors (e.g., PTHrP, CXCR4, SDF1, TGF B and RANKL) in breast and prostate cancer and multiple myeloma metastasis to bone. Finally, interaction of bone marrow stromal cells with multiple myeloma cells has been shown to contribute to the development of drug resistance.......................