The Use of Second Harmonic Generation to Image the Extracellular Matrix During Tumor Progression

Burke, Kathleen A.; Brown, Edward B.

doi:10.4161/21659087.2014.984509

Cited by 21 publications

(18 citation statements)

References 76 publications

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“…In addition, we further investigated the expression of MMPs ( Figure ), enzymes responsible for matrix degradation that have been shown to play a significant role in tumor progression . Indeed, the paracrine signaling among cancer cells and fibroblasts induce the latter in producing MMPs, that in turn can aid the migration of cancer cells the 3D environment.…”

Section: Resultsmentioning

confidence: 99%

“…Multiphoton microscopy and SHG are widely used in clinical applications as potential diagnostic parameters. In particular, SHG signal gets information concerning both the collagen composition and its structural modifications due to the transition of fibroblasts from a healthy to an activated state . In Figure A–C is reported the quantification of the ECM components: fibronectin (Figure A), HA (Figure B), and collagen (Figure C) in NF‐, CAF‐, and AC‐μTP.…”

Section: Resultsmentioning

confidence: 99%

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An Engineered Breast Cancer Model on a Chip to Replicate ECM‐Activation In Vitro during Tumor Progression

Gioiella

Urciuolo

Imparato

et al. 2016

Adv Healthcare Materials

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In this work, a new model of breast cancer is proposed featuring both epithelial and stromal tissues arranged on a microfluidic chip. The main task of the work is the in vitro replication of the stromal activation during tumor epithelial invasion. The activation of tumor stroma and its morphological/compositional changes play a key role in tumor progression. Despite emerging evidences, to date the activation of tumor stroma in vitro has not been achieved yet. The tumor-on-chip proposed in this work is built in order to replicate the features of its native counterpart: multicellularity (tumor epithelial cell and stromal cell); 3D engineered stroma compartment composed of cell-assembled extracellular matrix (ECM); reliable 3D tumor architecture. During tumor epithelial invasion the stroma displayed an activation process at both cellular and ECM level. Similarly of what repeated in vivo, ECM remodeling is found in terms of hyaluronic acid and fibronectin overexpression in the stroma compartment. Furthermore, the cell-assembled ECM featuring the stromal tissue, allowed on-line monitoring of collagen remodeling during stroma activation process via real time multiphoton microscopy. Also, trafficking of macromolecules within the stromal compartment has been monitored in real time.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

An Engineered Breast Cancer Model on a Chip to Replicate ECM‐Activation In Vitro during Tumor Progression

Gioiella

Urciuolo

Imparato

et al. 2016

Adv Healthcare Materials

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“…Previous studies also have shown that inhibition of LOX activity reduces the abundance of linear collagen fibrils associated with tumors (30). Using second harmonic generation imaging microscopy (30)(31)(32), we investigated whether the loss of ATP7A reduced collagen fibril assembly in primary tumors and metastatic lung nodules. As expected, tumor-associated collagen was predominantly organized in long linear arrangements (>30 μm) in 4T1-WT tumors, but in C3/ATP7A− derived tumors, the collagen fibrils were significantly shorter and exhibited an overall reduced linear organization (SI Appendix, Fig.…”

Section: Atp7a Deletion In 4t1 Breast Cancer Cells Attenuates Tumor Gmentioning

confidence: 99%

ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis

Shanbhag

Jasmer

Zhu

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

128

109

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Lysyl oxidase (LOX) and LOX-like (LOXL) proteins are copperdependent metalloenzymes with well-documented roles in tumor metastasis and fibrotic diseases. The mechanism by which copper is delivered to these enzymes is poorly understood. In this study, we demonstrate that the copper transporter ATP7A is necessary for the activity of LOX and LOXL enzymes. Silencing of ATP7A inhibited LOX activity in the 4T1 mammary carcinoma cell line, resulting in a loss of LOX-dependent mechanisms of metastasis, including the phosphorylation of focal adhesion kinase and myeloid cell recruitment to the lungs, in an orthotopic mouse model of breast cancer. ATP7A silencing was also found to attenuate LOX activity and metastasis of Lewis lung carcinoma cells in mice. Metaanalysis of breast cancer patients found that high ATP7A expression was significantly correlated with reduced survival. Taken together, these results identify ATP7A as a therapeutic target for blocking LOX-and LOXL-dependent malignancies.breast cancer | lung cancer | copper | lysyl oxidase | metastasis

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“…It has been shown that the imaging tests before surgery such as CT and MRI were not suitable for the detection of micrometastases and nodules (< 5 mm) (17); due to the in ltration of cancer tissues, lack of differentiation, nerve involvement and complex veins. The characteristics of the tube system and other characteristics are based on the surgeon's inspection and palpation, leading to a signi cant tumor residual rate (exceeding 50%) (18). Through the high permeability and high retention (EPR) effect of tumor tissue, uorescent dyes can accumulate in tumor tissue, NIRF imaging system could provide high tumor background signal ratio using large amounts of ICG, thereby helping surgeons to effectively localize tumors.…”

Section: Discussionmentioning

confidence: 99%

Unexpected Detection of a Sub-millimeter Early Hepatocellular Carcinoma Focus by Intraoperative Near-infrared Fluorescence Imaging

Dai

Wang

Lü

et al. 2020

Preprint

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Background: Intraoperative near-infrared fluorescence (NIRF) imaging became a great assistance to surgeons for precision cancer surgeries. Here, we demonstrate that NIRF was capable of detecting ultra-small hepatocellular carcinoma focus of about 430µm during real time monitored liver cancer surgery. Prognosis of hepatocellular carcinoma is closely related to residual tumor cells and tissues after tumor resection. Thus, close monitoring to ensure a complete removal of residual tumor is primordial. However, up to now, the identification of tiny lesions has not been reported. Herein, we report our findings about a case where tiny lesions were successfully identified by real-time ICG-NIRF imaging. Case presentation: A 55-year-old man, with chronic hepatitis B infection, was preoperatively diagnosed with liver space-occupying lesion. A fluorescence signal was detected on the surface of the liver through the NIRF imaging system. We then tested the residual liver surface and observed a high signal point, less than 1 mm in the right anterior lobe of the liver. Histopathological examination revealed that the tiny fluorescent spot belongs to an early hepatocellular carcinoma focus. Conclusion: Results strongly suggest that ICG-NIRF imaging system should be used as a routine intraoperative detection method for liver cancer surgery, in order to remove any residual tumor cells and tissue, hence minimizing further risk of remnant tumor regrowth.

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The Use of Second Harmonic Generation to Image the Extracellular Matrix During Tumor Progression

Cited by 21 publications

References 76 publications

An Engineered Breast Cancer Model on a Chip to Replicate ECM‐Activation In Vitro during Tumor Progression

An Engineered Breast Cancer Model on a Chip to Replicate ECM‐Activation In Vitro during Tumor Progression

ATP7A delivers copper to the lysyl oxidase family of enzymes and promotes tumorigenesis and metastasis

Unexpected Detection of a Sub-millimeter Early Hepatocellular Carcinoma Focus by Intraoperative Near-infrared Fluorescence Imaging

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