imaging technology is becoming
an increasing popular tool to visualize real-time cellular events in the tumor
microenvironment during metastatic progression. In the AACR 2012 symposium
entitled, “Immune Cell Function and Cancer In Vivo: Visualizing Friends
and Foes”, there were two remarkable presentations showing stunning
real-time revelations on the role of immune cells in
First, Dr. John Condeelis used multiphoton microscopy in a mammary imaging window to monitor macrophage and tumor cell interactions in a metastatic mouse PYMT breast cancer model. His videos revealed a stunning array of “streaming chemotaxis” in which macrophages and cancer cells are alternatively lined up in a stream during their trafficking to the nearby blood vessels. Condeelis further revealed clusters of macrophages along the blood vessels that are colocalized with the site to tumor cell intravasation, suggesting the integral role of macrophages in the cancer cell’s journey into circulation. This concept was supported by similar in vivo monitoring of PYMT mice defective in CSF production (macrophage-deficient), revealing that the absence of macrophages resulted in a significant reduction in streaming chemotaxis and intravasation. Condeelis further concluded his talk with the potential molecular mechanism underlying the effects of macrophages on metastasis.
Departing from Condeelis’ theme is the talk by Dr. Christopher Contag, who used real-time whole-body tracing to track the synergistic tumor-killing activity of cytokine-induced killer (CIK) cells and oncolytic vaccinia virus (vv) in a mouse xenograft model of ovarian cancer. CIK cells can kill tumor cells specifically by targeting the cancer-specific marker NKG2D (stress associated antigen). Using a combination of bioluminescent imaging (for vaccinia virus expressing luciferase reporter) and far red cy5.5 fluorescence imaging (for cy5.5 conjugated CIK cells), Contag discovered that CIK cells serve as an effective delivery vessel for vaccinia virus- enhancing the delivery of vaccinia virus specifically to the tumor site. Importantly, CIKs must be pre-infected with vaccinia virus, and that vaccinia virus must be delivered by CIKs, in order to achieve this level tumor specificity, suggesting remarkable synergy between CIKs and vaccinia virus.
These breathtaking studies are the few examples showing how powerful in vivo imaging technologies have revolutionized cancer research. Gone are the old school methods that produce “still” evidence of cancer progression. These new technologies allow scientists to perceive the cellular events governing cancer metastasis, or to trace the effectiveness of new anti-cancer treatments; all with real-time and single-cell clarity.
Details about technologies
highlighted in the AACR in vivo imaging seminar can be found below
1) Dr. Contag’s newest implantable confocal microscope featuring 3D YZ and XY stacked tumor videos, as well as Pulse Electron Avalanche Knife tissue sampler to allow concise and accurate tissue sampling. Dr. Contag is the Director of the Stanford Center for Photomedicine: http://med.stanford.edu/profiles/mips/researcher/Christopher_Contag/
2) Evrogen’s far red fluorescent reporters demonstrating low long-term cytotoxicity, and is ideal for tracing cancer cell metastasis and their susceptibility to treatments. More information about this technology can be found at http://www.nature.com/nmeth/journal/v6/n5/pdf/nmeth.f.249.pdf