Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2

Shen, Duanwen; Xu, Baogang; Liang, Kexian; Tang, Rui; Sudlow, Gail; Egbulefu, Christopher; Guo, Kevin; Som, Avik; Gilson, Rebecca C.; Maji, Dolonchampa; Mondal, Suman B.; Habimana-Griffin, LeMoyne; Akers, Walter J.; Li, Shunqiang; Liu, Yang; Bloch, Sharon; Kurkure, Sid; Nussinov, Zohar; Seidel, Alexander; Tsen, Shaw-Wei D.; Achilefu, Samuel

doi:10.1038/s41551-020-0528-7

Cited by 37 publications

(40 citation statements)

References 54 publications

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“…Annexin A2 has been proposed as a potential biomarker and therapeutic target for aggressive and metastatic cancers [72,73]. A recent study by Shen et al even postulated the use of phosphorylated Annexin A2 for the selective imaging of solid tumors within the clinic [74]. Studies by Sharma et al [58] and Yeatman et al [75] have actually shown that the expression of Annexin A2 is higher in metastatic cancer cell lines versus non-metastatic cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Mahdi

Malacrida

Nolan

et al. 2020

Cells

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When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.

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Section: Discussionmentioning

confidence: 99%

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Mahdi

Malacrida

Nolan

et al. 2020

Cells

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“…In general, contrast agents that have short half-lives (minutes) may not be suitable for MIGS for logistic reasons, including time from the imaging suite to the OR. An ideal agent for surgical guidance is expected to accumulate rapidly in tumors, have high tumor-to-background contrast, and be retained in this state for at least 4 h. The ability to optimize the pharmacokinetics of small-and medium-sized molecules such as peptides (15)(16)(17) and antibody fragments (18) makes them attractive for this purpose. Although some researchers have argued against the use of antibodies for imaging applications because of the long circulation time (up to 7 d), recent studies have leveraged the exceptional high tumor-associated receptors to identify small lesions (19).…”

Section: Exogenous Contrastmentioning

confidence: 99%

“…Raman Scattering (16) Raman scattering describes energy transfer between a photon and a vibrational mode in a molecule that results in a characteristic loss or gain of energy depending on the molecular bond and vibrational mode type. Plotting the energy difference between the incident light on the sample and the Raman-scattered light creates a Raman spectrum, sometimes referred to as a fingerprint, with varying intensities across the spectrum based on molecular content.…”

Section: Fluorescencementioning

confidence: 99%

Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery

et al. 2020

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Gone are the days when medical imaging was used primarily to visualize anatomic structures. The emergence of molecular imaging (MI), championed by radiolabeled 18 F-FDG PET, has expanded the information content derived from imaging to include pathophysiologic and molecular processes. Cancer imaging, in particular, has leveraged advances in MI agents and technology to improve the accuracy of tumor detection, interrogate tumor heterogeneity, monitor treatment response, focus surgical resection, and enable image-guided biopsy. Surgeons are actively latching on to the incredible opportunities provided by medical imaging for preoperative planning, intraoperative guidance, and postoperative monitoring. From label-free techniques to enabling cancer-selective imaging agents, imageguided surgery provides surgical oncologists and interventional radiologists both macroscopic and microscopic views of cancer in the operating room. This review highlights the current state of MI and sensing approaches available for surgical guidance. Salient features of nuclear, optical, and multimodal approaches will be discussed, including their strengths, limitations, and clinical applications. To address the increasing complexity and diversity of methods available today, this review provides a framework to identify a contrast mechanism, suitable modality, and device. Emerging low-cost, portable, and user-friendly imaging systems make the case for adopting some of these technologies as the global standard of care in surgical practice.

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“…Cancer-associated broblasts constitute the major component of breast cancer stroma (36,37). Through the broblast-tumor cell signaling axis, cancer cells can migrate, escape treatment and develop resistance.…”

Section: Nanocaco 3 Do Not Inhibit Broblast Growth But Do Affect Tummentioning

confidence: 99%

Calcium Carbonate Nanoparticles Stimulate Cancer Cell Reprogramming to Suppress Tumor Growth and Invasion in an Organ-on-a-chip System

Lam

Bishop

Mintz

et al. 2020

Preprint

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The acidic microenvironment of solid tumors induces the propagation of highly invasive and metastatic phenotypes. However, simulating these conditions in animal models present challenges that confound the effects of pH modulators on tumor progression. To recapitulate the tumor microenvironment and isolate the effect of pH on tumor viability, we developed a bifurcated microfluidic device that supports two different cell environments for direct comparison. RFP-expressing breast cancer cells (MDA-MB-231) were cultured in treatment and control chambers surrounded by fibrin, which received acid-neutralizing CaCO3 nanoparticles (nanoCaCO3) and cell culture media, respectively. Data analysis revealed that nanoCaCO3 buffered the pH within the normal physiological range and inhibited tumor cell proliferation compared to the untreated control (p < 0.05). Co-incubation of cancer cells and fibroblasts, followed by nanoCaCO3 treatment showed that the nanoparticles selectively inhibited the growth of the MDA-MB-231 cells and reduced cellular migration of these cells with no impact on the fibroblasts. Sustainable decrease in the intracellular pH of cancer cells treated with nanoCaCO3 indicates that the extracellular pH induced cellular metabolic reprogramming. These results suggest that the nanoCaCO3 can restrict the aggressiveness of tumor cells without affecting the growth and behavior of the surrounding stromal cells.

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Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2

Cited by 37 publications

References 54 publications

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers

Repurposing Molecular Imaging and Sensing for Cancer Image–Guided Surgery

Calcium Carbonate Nanoparticles Stimulate Cancer Cell Reprogramming to Suppress Tumor Growth and Invasion in an Organ-on-a-chip System

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