Abstract
Remodelling of collagen fibers has been described during every phase of cancer genesis and progression. Changes in morphology and organization of collagen fibers contribute to the formation of microenvironment that favors cancer progression and development of metastasis. However, there are only few data about remodelling of collagen fibers in healthy looking mucosa distant from the cancer. Using SHG imaging, electron microscopy and specialized softwares (CT-FIRE, CurveAlign and FiberFit), we objectively visualized and quantified changes in morphology and organization of collagen fibers and investigated possible causes of collagen remodelling (change in syntheses, degradation and collagen cross-linking) in the colon mucosa 10 cm and 20 cm away from the cancer in comparison with healthy mucosa. We showed that in the lamina propria this far from the colon cancer, there were changes in collagen architecture (width, straightness, alignment of collagen fibers and collagen molecules inside fibers), increased representation of myofibroblasts and increase expression of collagen-remodelling enzymes (LOX and MMP2). Thus, the changes in organization of collagen fibers, which were already described in the cancer microenvironment, also exist in the mucosa far from the cancer, but smaller in magnitude.
Highlights
Remodelling of collagen fibers has been described during every phase of cancer genesis and progression
On second harmonic generation (SHG) images, in the lamina propria of healthy patients, collagen fibers were wavy, orderly organized throughout lamina propria and around the crypts (Fig. 1a)
By analyzing whole SHG images using CT-FIRE software (Fig. 2a,b; 23–25), we have shown that there was a statistically significant increase in the width of collagen fibers in the lamina propria of the colon mucosa at a distance 10 cm (p = 0.032) and 20 cm from the tumor (p = 0.021), compared with healthy subjects (Fig. 2e)
Summary
Remodelling of collagen fibers has been described during every phase of cancer genesis and progression. Changes in morphology and organization of collagen fibers contribute to the formation of microenvironment that favors cancer progression and development of metastasis. Representation, and organization of collagen fibers contribute to the formation of the microenvironment that favors tumor progression, primarily through its effect on cell migration and polarization[12]. In the previous study of uninvolved colon mucosa[22], we described changes in the representation and organization of collagen fibers as far as 10 cm and 20 cm away from the colon cancer. The aim of our study was to quantify morphological parameters and organization of collagen fibers and to investigate possible causes of collagen remodelling (change in syntheses, degradation and collagen cross-linking) in the colon mucosa 10 cm and 20 cm away from the cancer in comparison with healthy mucosa. We showed that this far from the colon cancer there are changes in collagen architecture, increased representation of myofibroblasts and increase expression of collagen-remodelling enzymes
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