Fourier Transform Infrared Polarization Contrast Imaging Recognizes Proteins Degradation in Lungs upon Metastasis from Breast Cancer.

Abstract

Simple SummarySeveral lung extracellular matrix (ECM) proteins are involved in the formation of a metastatic niche in pulmonary metastasis and they accompany the cancer progression. Its gradual remodeling does not induce compositional changes of its components, but it is related to the re-distribution of individual proteins, their cross-linking and spatial arrangement within the tissue. The combination of FTIR and FTIR polarization contrast (PCI) imaging, as rapid, non-destructive, and label-free techniques, allows for the determination of protein alternations occurring in lungs that are affected by breast cancer metastasis. Both have the potential to characterize biochemical changes of the metastatic target, can determine phenotypes of tissue structures, and deliver a novel spectroscopic marker panel for the recognition of metastasis environment.The current understanding of mechanisms underlying the formation of metastatic tumors has required multi-parametric methods. The tissue micro-environment in secondary organs is not easily evaluated due to complex interpretation with existing tools. Here, we demonstrate the detection of structural modifications in proteins using emerging Fourier Transform Infrared (FTIR) imaging combined with light polarization. We investigated lungs affected by breast cancer metastasis in the orthotopic murine model from the pre-metastatic phase, through early micro-metastasis, up to an advanced phase, in which solid tumors are developed in lung parenchyma. The two IR-light polarization techniques revealed, for the first time, the orientational ordering of proteins upon the progression of pulmonary metastasis of breast cancer. Their distribution was complemented by detailed histological examination. Polarized contrast imaging recognised tissue structures of lungs and showed deformations in protein scaffolds induced by inflammatory infiltration, fibrosis, and tumor growth. This effect was recognised by not only changes in absorbance of the spectral bands but also by the band shifts and the appearance of new signals. Therefore, we proposed this approach as a useful tool for evaluation of progressive and irreversible molecular changes that occur sequentially in the metastatic process.