Abstract
In cancer biology, there has been a recent effort to understand tumor formation in the context of the tissue microenvironment. In particular, recent progress has explored the mechanisms behind how changes in the cell-extracellular matrix ensemble influence progression of the disease. The extensive use of in vitro tissue culture models in simulant matrix has proven effective at studying such interactions, but modalities for non-invasively quantifying aspects of these systems are scant. We present the novel application of an imaging technique, Inverse Spectroscopic Optical Coherence Tomography, for the non-destructive measurement of in vitro biological samples during matrix remodeling. Our findings indicate that the nanoscale-sensitive mass density correlation shape factor D of cancer cells increases in response to a more crosslinked matrix. We present a facile technique for the non-invasive, quantitative study of the micro- and nano-scale structure of the extracellular matrix and its host cells.
Highlights
Colon cancer is the third-most prevalent cause of new cancer cases and cancer-related deaths in the U.S, with an estimated 93,090 new cases expected to be diagnosed in 2015 (American Cancer Society 2015)
In the tumor microenvironment studies using second harmonic generation microscopy (SHG) have shown transformation of collagen structure in tumors compared to healthy tissue, with extracellular matrix (ECM) in tumors displaying a higher orientation of collagen fibers and thicker fiber bundles indicative of crosslinking (Chen et al 2012, Nadiarnykh et al 2010, Zhuo et al 2009)
We show the sensitivity of Inverse Spectroscopic Optical Coherence Tomography (ISOCT) to enzymatic collagen crosslinking, as well as present it as a technique to study the structural phenotype of cells, as reflected by the response of colon cancer cells to a crosslinked collagen substrate
Summary
Colon cancer is the third-most prevalent cause of new cancer cases and cancer-related deaths in the U.S, with an estimated 93,090 new cases expected to be diagnosed in 2015 (American Cancer Society 2015). Interactions between cells and the extracellular matrix (ECM) have been implicated in promotion of tumor growth and progression in many types of cancer (Lu et al 2012, Nelson and Bissell 2006, Dvorak et al 2011, Chaudhuri et al 2014, Peddareddigari et al 2010, Cox and Erler 2011, Barcus et al 2013, Pickup et al 2014, Zou et al 2013). In the tumor microenvironment studies using second harmonic generation microscopy (SHG) have shown transformation of collagen structure in tumors compared to healthy tissue, with ECM in tumors displaying a higher orientation of collagen fibers and thicker fiber bundles indicative of crosslinking (Chen et al 2012, Nadiarnykh et al 2010, Zhuo et al 2009)
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