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

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.

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Tracking Extracellular Matrix Remodeling in Lungs Induced by Breast Cancer Metastasis. Fourier Transform Infrared Spectroscopic Studies

Molecules ◽

10.3390/molecules25010236 ◽

2020 ◽

Vol 25 (1) ◽

pp. 236 ◽

Cited By ~ 3

Author(s):

Karolina Chrabaszcz ◽

Katarzyna Kaminska ◽

Karolina Augustyniak ◽

Monika Kujdowicz ◽

Marta Smeda ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Fourier Transform ◽

Cancer Metastasis ◽

Fourier Transform Infrared ◽

Muscle Cells ◽

Breast Cancer Metastasis ◽

Extracellular Matrix Remodeling ◽

Matrix Remodeling ◽

Large Area

This work focused on a detailed assessment of lung tissue affected by metastasis of breast cancer. We used large-area chemical scanning implemented in Fourier transform infrared (FTIR) spectroscopic imaging supported with classical histological and morphological characterization. For the first time, we differentiated and defined biochemical changes due to metastasis observed in the lung parenchyma, atelectasis, fibrous, and muscle cells, as well as bronchi ciliate cells, in a qualitative and semi-quantitative manner based on spectral features. The results suggested that systematic extracellular matrix remodeling with the progress of the metastasis process evoked a decrease in the fraction of the total protein in atelectasis, fibrous, and muscle cells, as well as an increase of fibrillar proteins in the parenchyma. We also detected alterations in the secondary conformations of proteins in parenchyma and atelectasis and changes in the level of hydroxyproline residues and carbohydrate moieties in the parenchyma. The results indicate the usability of FTIR spectroscopy as a tool for the detection of extracellular matrix remodeling, thereby enabling the prediction of pre-metastatic niche formation.

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Breast cancer and incidence of non-caseating granulomas diagnosed in PET avid chest lymphadenopahy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12549 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12549-e12549

Author(s):

Rabih Bechara ◽

Patricia Rich ◽

Christopher Parks ◽

Dacian Bonta ◽

Ioana Bonta

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Cancer Metastasis ◽

Early Stage ◽

Lung Parenchyma ◽

Breast Cancer Metastasis ◽

Current Treatment ◽

Endobronchial Ultrasound ◽

Breast Cancer Patients ◽

Caseating Granuloma

e12549 Background: Breast cancer is known to metastasize to the lung parenchyma and lymph nodes. Most breast malignancies are clinically staged using radiographic modalities (e.g. PET scans). Importantly, several inflammatory disorders will present lymph node FDG-uptake on PET, which can be mistaken for breast cancer metastasis. This may alter staging and implicitly treatment for individuals within whom both undiagnosed autoimmune disorders and breast cancer co-occur. We aim to examine the frequency of non-caseating granulomas diagnosed in PET avid mediastinal/hilar nodes in patients with known breast cancer. Methods: Between March 2013 and December 2015, 46 women diagnosed with breast cancer were staged by PET-CT. Those with positive result in the mediastinum/hilum underwent linear endobronchial ultrasound (EBUS) for pathologic diagnosis and ensuing treatment Results: Of the 46 patients with avid mediastinal/hilar adenopathy, 31 (67%) had malignant cytology on EBUS; the remaining 15 had positive PET but negative cytology for malignancy. Twelve of the 15 patients with false positive PET had reactive lymph nodes, and 3 had non-caseating granulomas on cytology (see table). Twenty percent of the patients with negative cytology and positive PET had non-caseating granuloma, and 6.5 % of all patients with positive PET had non-caseating granulomas. Conclusions: To our knowledge, this study represents the largest cohort of breast cancer patients, where the incidence of non-caseating granulomas is investigated in PET-positive mediastinal/hilar nodes. We conclude that in selected patients, in addition to imaging, pathologic staging should be done. Also, the finding of non-caseating granulomas in these patients may either indicate an incidental diagnosis of early stage sarcoidosis, or an inflammatory reaction to the current treatment (sarcomatoid reaction). We also suggest that these patients should be followed for any manifestations of sarcoidosis. [Table: see text]

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