Novel insights into breast cancer progression and metastasis: A multidisciplinary opportunity to transition from biology to clinical oncology

Scimeca, Manuel; Urbano, Nicoletta; Bonfiglio, Rita; Duggento, Andrea; Toschi, Nicola; Schillaci, Orazio; Bonanno, Elena

doi:10.1016/j.bbcan.2019.07.002

Cited by 39 publications

(26 citation statements)

References 100 publications

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“…Even though this can be considered a pilot experimental study, data reported here can provide the scientific rationale for further large-cohort population clinical studies that aim to identify SUV cut-off values for the in vivo early detection of prostate lesions with a high propensity to form bone metastasis. Indeed, as mentioned above, numerous investigations demonstrated the negative prognostic significance of the expression of bone biomarkers in human neoplasia such as prostate and breast cancers [9,10,12,17,20,30,33,35]. Specifically, the expression of these biomarkers has been associated with the development of bone metastasis within 5 years from histological diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies emphasized the needed for innovative multidisciplinary approaches to address the new challenges of cancer medicine [15,16,17]. In particular, great relevance has been given to the collaboration between imaging diagnostics and anatomic pathology departments [17,18,19,20,21]. The comparison and sharing of data derived by imaging procedures and histopathological analysis can shed new light on cancer mechanisms, thus providing useful information for the development and/or revaluation of diagnostic analyses.…”

Section: Discussionmentioning

confidence: 99%

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18F–Choline PET/CT Identifies High-Grade Prostate Cancer Lesions Expressing Bone Biomarkers

Urbano

Scimeca

Crocco

et al. 2019

JCM

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The main aim of this study was to investigate the possible association between 18F–choline uptake and histopathological features of prostate biopsies such as the Gleason Group and the expression of both epithelial to mesenchymal transition (vimentin) and bone mineralization (bone morphogenetics protein (BMP)-2, runt-related transcription factor 2 (RUNX2), receptor activator of nuclear factor-κB ligand (RANKL), vitamin D receptor (VDR), and pentraxin 3 (PTX3) in situ biomarkers. To this end, we enrolled 79 consecutive prostate cancer patients that underwent both the 18F–choline PET/CT analysis and the prostate bioptic procedure. The standardized uptake value (SUV) average values were collected from 18F–choline PET/CT analysis whereas Gleason Group and immunostaining data were collected from paraffin-embedded sections. Histological classification showed a heterogenous population including both low/intermediate and high-grade prostate cancers. A significant increase of 18F–choline uptake in high-grade prostate lesions (Gleason Score ≥8) was found. Also, linear regression analysis showed a significant correlation between 18F–choline uptake and the number of vimentin, RANKL, VDR, or PTX3 positive prostate cancer cells. Conversely, we observed no significant association between 18F–choline uptake and the expression of bone biomarkers involved in the early phases of osteoblast differentiation (BMP-2, RUNX2). In conclusion, results here reported can lay the foundation for the use of 18F–choline positron emission tomography (PET)/computed tomography (CT) as a diagnostic tool capable of identifying high-grade prostate cancer lesions expressing bone biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

18F–Choline PET/CT Identifies High-Grade Prostate Cancer Lesions Expressing Bone Biomarkers

Urbano

Scimeca

Crocco

et al. 2019

JCM

Self Cite

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“…Breast cancer cells have strong invasive ability and often form distant metastases (3,4). Despite the great progress achieved in therapeutics, relapse and metastasis are still the leading reasons for death in breast cancer patients (5). Therefore, finding specific molecules which can serve as markers for early diagnosis and prognosis and can become therapeutic targets has become an important research direction.…”

Section: Introductionmentioning

confidence: 99%

miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2

Liu

Jin

et al. 2020

Front. Oncol.

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MicroRNAs (miRNAs) can participate in many behaviors of various tumors. Prior studies have reported that miR-15b-5p in different tumors can either promote or inhibit tumor progression. In breast cancer, the role of miR-15b-5p is unclear. The main objective of this paper is to explore miR-15b-5p effects and their mechanisms in breast cancer using both in vitro and in vivo experiments. This study showed that miR-15b-5p expression was upregulated in breast cancer compared with normal breast tissue and was positively correlated with poor overall survival in patients. Knockdown of miR-15b-5p in MCF-7 and MD-MBA-231 breast cancer cells restrained cell growth and invasiveness and induced apoptosis, whereas overexpression of miR-15b-5p achieved the opposite effects. We next revealed a negative correlation between miR-15b-5p and heparanase-2 (HPSE2) expression in breast cancer. Knockdown of miR-15b-5p significantly increased HPSE2 expression at both mRNA and protein levels in breast cancer cells in vitro. The underlying mechanisms of miR-15-5p in breast cancer were investigated using luciferase activity reporter assay and rescue experiments. In addition, miR-15b-5p knockdown significantly inhibited tumor growth in a xenograft model in mice. In summary, we showed that miR-15b-5p promotes breast cancer cell proliferation, migration, and invasion by directly targeting HPSE2. Accordingly, miR-15b-5p may serve both as a tool for prognosis and as a target for therapy of breast cancer patients.

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“…21 Breast cancer is a common disease with high morbidity and mortality in females worldwide, which has marked characteristics of high heterogeneous, high metastasis rate, high recurrence rate, poor survival and poor prognosis. 45 Chemotherapy remains the main therapeutic method in breast cancer, but it is often ineffective as drug resistance occurs easily and quickly for long time use. Immunotherapy strategies are becoming the newly promising therapeutic options.…”

Section: Discussionmentioning

confidence: 99%

<p>Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells</p>

Huang¹,

Zhao²,

Wei³

et al. 2020

IJN

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Background and Aim: We have previously identified ubiquitinated proteins (UPs) from tumor cell lysates as a promising vaccine for cancer immunotherapy in different mouse tumor models. In this study, we aimed at developing a highly efficient therapeutic adjuvant built-in nanovaccine (α-Al 2 O 3-UPs) by a simple method, in which UPs from tumor cells could be efficiently and conveniently enriched by α-Al 2 O 3 nanoparticles covalently coupled with Vx3 proteins (α-Al 2 O 3-CONH-Vx3). Methods: The α-Al 2 O 3 nanoparticles were modified with 4-hydroxybenzoic acid followed by coupling with ubiquitin-binding protein Vx3. It was then used to enrich UPs from 4T1 cell lysate. The stability and the efficiency for the UPs enrichment of α-Al 2 O 3-CONH-Vx3 were examined. The ability of α-Al 2 O 3-UPs to activate DCs was examined in vitro subsequently. The splenocytes from the vaccinated mice were re-stimulated with inactivated tumor cells, and the IFN-γ secretion was detected by ELISA and flow cytometry. Moreover, the therapeutic efficacy of α-Al 2 O 3-UPs, alone and in combination with chemotherapy, was examined in 4T1 tumor-bearing mice. Results: Our results showed that α-Al 2 O 3-UPs were successfully synthesized and abundant UPs from tumor cell lysate were enriched by the new method. In vitro study showed that compared to the physical mixture of α-Al 2 O 3 nanoparticles and UPs (α-Al 2 O 3 +UPs), α-Al 2 O 3-UPs stimulation resulted in higher upregulations of CD80, CD86, MHC class I, and MHC class II on DCs, indicating the higher ability of DC activation. Moreover, α-Al 2 O 3-UPs elicited a more effective immune response in mice, demonstrated by higher IFN-γ secretion than α-Al 2 O 3 +UPs. Furthermore, α-Al 2 O 3-UPs also exhibited a more potent effect on tumor growth inhibition and survival prolongation in 4T1 tumor-bearing mice. Notably, when in combination with low dose chemotherapy, the anti-tumor effect was further enhanced, rather than using α-Al 2 O 3-UPs alone. Conclusion: This study presents an adjuvant built-in nanovaccine generated by a new simple method that can be potentially applied to cancer immunotherapy and lays the experimental foundation for future clinical application.

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Novel insights into breast cancer progression and metastasis: A multidisciplinary opportunity to transition from biology to clinical oncology

Cited by 39 publications

References 100 publications

18F–Choline PET/CT Identifies High-Grade Prostate Cancer Lesions Expressing Bone Biomarkers

18F–Choline PET/CT Identifies High-Grade Prostate Cancer Lesions Expressing Bone Biomarkers

miR-15b-5p Promotes Growth and Metastasis in Breast Cancer by Targeting HPSE2

<p>Anti-Tumor Efficacy of an Adjuvant Built-In Nanovaccine Based on Ubiquitinated Proteins from Tumor Cells</p>

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