Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination

Fonseca, Nuno A.; Rodrigues, Ana Sofia; Rodrigues-Santos, Paulo; Alves, Vera; Gregório, Ana C.; Valério-Fernandes, Ângela; Gomes‐da‐Silva, Lígia C.; Rosa, Manuel Santos; Moura, Vera; Ramalho‐Santos, João; Simões, Sérgio; Moreira, João Nuno

doi:10.1016/j.biomaterials.2015.08.007

Cited by 77 publications

(65 citation statements)

References 56 publications

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“…In addition to its overexpression on a variety of cancer cells [243][244][245][246][247][251][252][253] and endothelial cells of the tumor vasculature 249,250 , nucleolin has been extensively implicated in mechanisms that promote metastatic progression 270,295,304,305,471 . Hence, it has become an attractive target for the therapeutic prevention of metastases.…”

Section: Discussionmentioning

confidence: 99%

“…Altogether, nucleolin's biological functions that contribute to cell homeostasis are also responsible for its role in the development of malignant traits under pathological conditions. In this respect, overexpression of nucleolin, and increased localization at the cell membrane, was shown in different cancer cell lines [243][244][245][246][247][248] and endothelial cells 249,250 , as well as in tumors of diverse histological origin [251][252][253][254][255][256][257][258][259] . Nucleolin overexpression contributes to tumorigenesis and cancer progression by supporting cancer cells proliferation and survival, and by promoting invasion and angiogenesis.…”

Section: Nucleolin: a New Perspective On Breast Cancer Needsmentioning

confidence: 98%

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Meeting the needs of breast cancer: A nucleolin’s perspective

Gregório

Lacerda

Figueiredo

et al. 2018

Critical Reviews in Oncology/Hematology

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A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival. Hence, nucleolin has emerged as a relevant target for therapeutic intervention in cancer malignancy, including breast cancer. This review focus on the contribution of nucleolin for cancer disease and on the development of therapeutic strategies targeting this protein. In this respect, it also provides a critical analysis about the potential and pitfalls of nanomedicine for cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Nucleolin: a New Perspective On Breast Cancer Needsmentioning

confidence: 98%

Meeting the needs of breast cancer: A nucleolin’s perspective

Gregório

Lacerda

Figueiredo

et al. 2018

Critical Reviews in Oncology/Hematology

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“…These results are in line with a recent study, in which Fonseca et al . reported efficient internalization of NCL-targeting liposomes by both breast cancer non-CSCs and CSCs [27]. Fonseca et al .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of somatostatin and nucleolin receptors for therapeutic delivery in non-small cell lung cancer stem cells applying the somatostatin-analog DOTATATE and the nucleolin-targeting aptamer AS1411

et al. 2017

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Cancer stem cells represent the putative tumor-driving subpopulation thought to account for drug resistance, relapse, and metastatic spread of epithelial and other cancer types. Accordingly, cell surface markers for therapeutic delivery to cancer stem cells are subject of intense research. Somatostatin receptor 2 and nucleolin are known to be overexpressed by various cancer types, which have elicited comprehensive efforts to explore their therapeutic utilization. Here, we evaluated somatostatin receptor 2 targeting and nucleolin targeting for therapeutic delivery to cancer stem cells from lung cancer. Nucleolin is expressed highly but not selectively, while somatostatin receptor 2 is expressed selectively but not highly by cancer cells. The non-small cell lung cancer cell lines A549 and H1299, displayed average levels of both surface molecules as judged based on analysis of a larger cell line panel. H1299 compared to A549 cells showed significantly elevated sphere-forming capacity, indicating higher cancer stem cell content, thus qualifying as suitable test system. Nucleolin-targeting 57Co-DOTA-AS1411 aptamer showed efficient internalization by cancer cells and, remarkably, at even higher efficiency by cancer stem cells. In contrast, somatostatin receptor 2 expression levels were not sufficiently high in H1299 cells to confer efficient uptake by either non-cancer stem cells or cancer stem cells. The data provides indication that the nucleolin-targeting AS1411 aptamer might be used for therapeutic delivery to non-small cell lung cancer stem cells.

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“…It is abnormally expressed in cancer cells and increased expression in many cancers, including breast cancer, is generally associated with poor prognosis [51]. Nucleolin is also overexpressed in breast cancer cell populations [52]. Our attempts to validate the interaction of cathepsin D with NHE1 by co-IP experiments were unsuccessful; validation of the other protein-protein interactions were not attempted at this time.…”

Section: Nhe1 and Signal Transduction Proteinsmentioning

confidence: 99%