Multiparametric Spectroscopic Photoacoustic Imaging of Breast Cancer Development in a Transgenic Mouse Model

Wilson, Katheryne E.; Bachawal, Sunitha V.; Tian, Lu; Willmann, Jürgen K.

doi:10.7150/thno.9922

Cited by 49 publications

(46 citation statements)

References 41 publications

(65 reference statements)

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“…PA imaging is relatively new to this field, but it offers a great deal of promise in being able to provide co-registered functional and structural information without any endogenous contrast [33, 49]. Within the resolution limits of our imaging system (45 μm axial, 90 μm lateral), PA imaging was capable of capturing the oxygenation of the blood up to a depth of 11 mm at 40 MHz.…”

Section: Discussionmentioning

confidence: 99%

“…However, most approaches have focused on engineering advances with the aim of improving the spatial resolution of the technique [31]. The application of PA imaging to the treatment monitoring problem has only begun recently with several encouraging studies demonstrating the potential of the technique for detecting changes of sO 2 in the tumor vasculature as a function of treatment [32] as well as during tumor development [33] and even imaging vascular perfusion [34]. …”

Section: Introductionmentioning

confidence: 99%

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Photoacoustic Imaging of Cancer Treatment Response: Early Detection of Therapeutic Effect from Thermosensitive Liposomes

et al. 2016

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Imaging methods capable of indicating the potential for success of an individualized treatment course, during or immediately following the treatment, could improve therapeutic outcomes. Temperature Sensitive Liposomes (TSLs) provide an effective way to deliver chemotherapeutics to a localized tumoral area heated to mild-hyperthermia (HT). The high drug levels reached in the tumor vasculature lead to increased tumor regression via the cascade of events during and immediately following treatment. For a TSL carrying doxorubicin (DOX) these include the rapid and intense exposure of endothelial cells to high drug concentrations, hemorrhage, blood coagulation and vascular shutdown. In this study, ultrasound-guided photoacoustic imaging was used to probe the changes to tumors following treatment with the TSL, HaT-DOX (Heat activated cytoToxic). Levels of oxygen saturation (sO2) were studied in a longitudinal manner, from 30 min pre-treatment to 7 days post-treatment. The efficacious treatments of HT-HaT-DOX were shown to induce a significant drop in sO2 (>10%) as early as 30 min post-treatment that led to tumor regression (in 90% of cases); HT-Saline and non-efficacious HT-HaT-DOX (10% of cases) treatments did not show any significant change in sO2 at these timepoints. The changes in sO2 were further corroborated with histological data, using the vascular and perfusion markers CD31 and FITC-lectin. These results allowed us to further surmise a plausible mechanism of the cellular events taking place in the TSL treated tumor regions over the first 24 hours post-treatment. The potential for using photoacoustic imaging to measure tumor sO2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Photoacoustic Imaging of Cancer Treatment Response: Early Detection of Therapeutic Effect from Thermosensitive Liposomes

et al. 2016

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“…Photoacoustic imaging of the mouse mammary tumor virus-polyoma middle T (MMTVPyMT)-driven breast cancer model demonstrated that transformation of normal breast tissue to invasive carcinoma resulted in a progressive decrease of cytoplasmic LD abundance (29). In line with this finding, pharmacological activation of peroxisome proliferatoractivated receptor-γ caused accumulation of LDs in breast cancer cells and decreased their proliferation (30).…”

Section: Significancementioning

confidence: 85%

CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation

Wright

Hou

et al. 2017

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

137

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Triple-negative breast cancer (TNBC) is notoriously aggressive with high metastatic potential, which has recently been linked to high rates of fatty acid oxidation (FAO). Here we report the mechanism of lipid metabolism dysregulation in TNBC through the prometastatic protein, CUB-domain containing protein 1 (CDCP1). We show that a "low-lipid" phenotype is characteristic of breast cancer cells compared with normal breast epithelial cells and negatively correlates with invasiveness in 3D culture. Using coherent anti-Stokes Raman scattering and two-photon excited fluorescence microscopy, we show that CDCP1 depletes lipids from cytoplasmic lipid droplets (LDs) through reduced acyl-CoA production and increased lipid utilization in the mitochondria through FAO, fueling oxidative phosphorylation. These findings are supported by CDCP1's interaction with and inhibition of acyl CoA-synthetase ligase (ACSL) activity. Importantly, CDCP1 knockdown increases LD abundance and reduces TNBC 2D migration in vitro, which can be partially rescued by the ACSL inhibitor, Triacsin C. Furthermore, CDCP1 knockdown reduced 3D invasion, which can be rescued by ACSL3 co-knockdown. In vivo, inhibiting CDCP1 activity with an engineered blocking fragment (extracellular portion of cleaved CDCP1) lead to increased LD abundance in primary tumors, decreased metastasis, and increased ACSL activity in two animal models of TNBC. Finally, TNBC lung metastases have lower LD abundance than their corresponding primary tumors, indicating that LD abundance in primary tumor might serve as a prognostic marker for metastatic potential. Our studies have important implications for the development of TNBC therapeutics to specifically block CDCP1-driven FAO and oxidative phosphorylation, which contribute to TNBC migration and metastasis.he transmembrane glycoprotein, CUB-domain containing protein 1 (CDCP1), is a driver of migration and invasion in multiple forms of carcinoma, including renal (1, 2), ovarian (3, 4), prostate (5), pancreatic (6, 7), colon (8-12), and triple-negative breast (TNBC) (13, 14) carcinomas, among others. Furthermore, CDCP1's role in tumor metastasis was confirmed in vivo in lung (15, 16), ovarian (17), prostate (5), and colon (9) cancers. Although CDCP1's role in TNBC metastasis has not been established to date, high CDCP1 expression has been validated as a prognostic marker of poor survival in TNBC when combined with positive node status (18).Our understanding of CDCP1's upstream regulators, its mechanism of activation, and downstream signaling continues to expand (recently reviewed in ref. 19). Studies by others (5) and our group (14) have demonstrated that CDCP1 cleavage is necessary for its activation, and recently, we have further shown that cleavage stimulates CDCP1 homodimerization (14). Homodimeric CDCP1 stimulates phosphorylation of protein kinase C δ (PKCδ) by Src kinase, leading to migration and invasion of TNBC cells in vitro (14). Adding to our knowledge of CDCP1's downstream signaling, we report that CDCP1 regulates lipid m...

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“…Hemoglobin dominates the absorption in tissues (except for melanin in the skin) with the highest optical absorption coefficient and therefore has been the focus of most of the studies of endogenous photoacoustic signal. By using multiple wavelengths of laser light (spectroscopic photoacoustic imaging), relative concentrations of specific chromophores can be determined (20)(21)(22)(23)(24)(25). A highly applied method, especially in cancer imaging, is to detect the relative amounts of deoxygenated (deoxy) and oxygenated (oxy) hemoglobin (Hb), from which the oxygen saturation (100% …”

Section: Photoacoustic Spectroscopymentioning

confidence: 99%

Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience

Valluru¹,

Wilson²,

Willmann³

2016

Radiology

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157

104

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Multiparametric Spectroscopic Photoacoustic Imaging of Breast Cancer Development in a Transgenic Mouse Model

Cited by 49 publications

References 41 publications

Photoacoustic Imaging of Cancer Treatment Response: Early Detection of Therapeutic Effect from Thermosensitive Liposomes

Photoacoustic Imaging of Cancer Treatment Response: Early Detection of Therapeutic Effect from Thermosensitive Liposomes

CDCP1 drives triple-negative breast cancer metastasis through reduction of lipid-droplet abundance and stimulation of fatty acid oxidation

Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience

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