Prostate Cancer Lecture 2.doc

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Anatomy and Cell Biology
Anatomy and Cell Biology 4461B
Geordie Shepherd

JL Lecture 2: The Role of Imaging in Prostate Cancer Research Metastasis 1. Clonal expansion, growth, diversification and angiogenesis 2. Migration through the basement membrane 3. Invasion through the extracellular matrix 4. Intravasation 5. Interaction with host blood cells 6. Formation of tumor embolus 7. Arrest in capillaries and adhesion to basement membrane 8. Extravasation 9. Metastatic deposit and growth in secondary organ Metastasis is extremely inefficient; less than 0.01 of cell that originated from the primary tumor actually metastasize. Models of Prostate Cancer Other than man, dog is the only animal known to have spontaneous high grade PIN • and prostate cancer and have similar disease characteristics including age of onset, metastasis and androgen independence Cell Culture Models • Some prostate cancer cell lines have androgen receptor signaling and are isolated from different areas of metastasis (lymph node, bone or brain) • 2D models - One part of the cell is attached to a dish, one part is exposed to medi- um • 3D models - Morphology changes dramatically when you add the cells to a 3D en- vironment Animal Models • Xenografts - can be subcutaneous or orthotopic (in the prostate). Location of the tumor affects tumor growth. • Genetic - allows investigators to generate accurate models of human malignancies through the expression of oncogenes, knock-in of genetic point mutations and knock-out of tumor suppressors central to the human malignancy studied. For ex. haploinsufficiency of PTEN is an early event in prostate tumorigenesis, resulting in the development of high-grade PIN. Complete loss of PTEN results in the progres- sion to an invasive prostate cancer. • Drosophila - Recent discoveries have showed us that... •Overexpression of myc leads to hyperproliferation of cells • Apoptosis-induced compensatory proliferation - apoptotic cells send prolif- eratory signals to neighbors to maintain tissue size • Cells that lack Scribble (maintains cell polarity) and have activated Ras are metastatic • Zebrafish • Easy to manipulate like Dropsophila and transparency is useful for fluores- cence • Sunitinib was tested in zebrafish • Tumor volume, disseminated tumor foci, averages of maximal dis- tances of metastatic foci and tumor vessel density were measured • Chick embryo - Organ is vascularized and provides gas exchange. If you in- ject tumor cells in the chick embryo, can see a dramatic increase in blood vessel growth. Chick embyros are useful because you can put them in a 3D timelapse confocal microscopy and visualize them for 72 hours. They don’t have to be maintained like a mouse. Imaging Modalities • Can be divided into those that rely on emissopn of energy from exogenously ad- ministered radioactive isotopes (ex. PET, SPECT) and those that rely on interac- tions between tissues and applied energy X-Ray Film • Map of the opaqueness of tissue to x-ray photons • Plain films are poor at detecting bone metastases because there must be a change in density of 50% before seen radiographically Bone Scan (Scintigraphy) • Patient injected with Tc-99m methylene diphosphonate and imaged using a gamma camera • Accumulation in tissue depend
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