Intracellular autofluorescence: a biomarker for epithelial cancer stem cells

Miranda-Lorenzo, Irene; Navarro‐Dorado, Jorge; Lonardo, Enza; Alcalá, Sonia; Serrano, Alicia G.; Clausell-Tormos, Jenifer; Cioffi, Michèle; Megı́as, Diego; Zagorac, Sladjana; Balic, Anamaria; Hidalgo, Manuel; Erkan, Mert; Kleeff, Jörg; Scarpa, Aldo; Sáinz, Bruno; Heeschen, Christopher

doi:10.1038/nmeth.3112

Cited by 173 publications

(194 citation statements)

References 35 publications

Supporting

Mentioning

185

Contrasting

Order By: Relevance

“…Because the cancer stem cell (CSC) hypothesis was functionally validated for leukemia in 1994 (7), convincing evidence has emerged for several solid tumors indicating that like adult tissues, tumors are sustained and promoted by cells that exhibit features of stem cells, including unlimited self-renewal (8). We and others have provided conclusive evidence for a hierarchical organization in human PDAC and, even more importantly, demonstrated that pancreatic CSCs, at the apex of the hierarchy, have exclusive tumorigenic and metastatic potential and are inherently resistant to chemotherapy (9)(10)(11). Indeed, the survival of such resistant CSCs during chemotherapy, despite initial tumor regression, represents a plausible explanation for the later fatal relapse of disease in most patients (3,4).…”

Section: Introductionmentioning

confidence: 78%

Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms

Cioffi

Trabulo

Hidalgo

et al. 2015

Clinical Cancer Research

Self Cite

173

138

View full text Add to dashboard Cite

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a cancer of the exocrine pancreas with unmet medical need and is strongly promoted by tumor-associated macrophages (TAM). The presence of TAMs is associated with poor clinical outcome, and their overall role, therefore, appears to be protumorigenic. The “don't eat me” signal CD47 on cancer cells communicates to the signal regulatory protein-α on macrophages and prevents their phagocytosis. Thus, inhibition of CD47 may offer a new opportunity to turn TAMs against PDAC cells, including cancer stem cells (CSC), as the exclusively tumorigenic population. Experimental Design: We studied in vitro and in vivo the effects of CD47 inhibition on CSCs using a large set of primary pancreatic cancer (stem) cells as well as xenografts of primary human PDAC tissue. Results: CD47 was highly expressed on CSCs, but not on other nonmalignant cells in the pancreas. Targeting CD47 efficiently enhanced phagocytosis of a representative set of primary human pancreatic cancer (stem) cells and, even more intriguingly, also directly induced their apoptosis in the absence of macrophages during long-term inhibition of CD47. In patient-derived xenograft models, CD47 targeting alone did not result in relevant slowing of tumor growth, but the addition of gemcitabine or Abraxane resulted in sustained tumor regression and prevention of disease relapse long after discontinuation of treatment. Conclusions: These data are consistent with efficient in vivo targeting of CSCs, and strongly suggest that CD47 inhibition could be a novel adjuvant treatment strategy for PDAC independent of underlying and highly variable driver mutations. Clin Cancer Res; 21(10); 2325–37. ©2015 AACR.

show abstract

Section: Introductionmentioning

confidence: 78%

Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms

Cioffi

Trabulo

Hidalgo

et al. 2015

Clinical Cancer Research

Self Cite

173

138

View full text Add to dashboard Cite

show abstract

“…Hoechst dye exclusion activity has also been described as a method to identify a cellular fraction termed the SP that contains tumorigenic stem/progenitor cells (Patrawala et al 2005). Finally, an autofluorescent epithelial CSC phenotype has recently been reported, however it still remains to be proven whether it can be used to identify BCSCs (Miranda-Lorenzo et al 2014).…”

Section: Breast Cancer Stem Cellsmentioning

confidence: 99%

The role of steroid hormones in breast cancer stem cells

Simões¹,

Alférez²,

Howell³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity.

show abstract

“…This new marker has been proven to be a more reliable and accurate way to identify and characterize CSCs. [16,23] Another important functional property of CSCs, as well as normal stem SCs, is the ability to produce sphere-forming colonies from a single cell in serum-free medium or in soft agar medium, as differentiated cells cannot survive and proliferate in this environment. [24] Thus, several studies have used the sphere formation assay as an efficient method for isolating, enriching and maintaining CSCs from various primary tumors.…”

Section: Cd38mentioning

confidence: 99%

Therapeutic strategies for targeting cancer stem cells

Kim¹,

Siegler²,

Siriwon³

et al. 2016

JCMT

View full text Add to dashboard Cite

The therapeutic limitations of conventional chemotherapeutic drugs present a challenge for cancer therapy; these shortcomings are largely attributed to the ability of cancer cells to repopulate and metastasize after initial therapies. Compelling evidence suggests that cancer stem cells (CSCs) have a crucial impact in current shortcomings of cancer therapy because they are largely responsible for tumor initiation, relapse, metastasis, and chemo-resistance. Thus, a better understanding of the properties and mechanisms underlying CSC resistance to treatments is necessary to improve patient outcomes and survival rates. In this review, the authors characterize and compare different CSC-specific biomarkers that are present in various types of tumors. We further discuss multiple targeting approaches currently in preclinical or clinical testing that show great potential for targeting CSCs. This review discusses numerous strategies to eliminate CSCs by targeting surface biomarkers, regulating CSC-associated oncogenes and signaling pathways, inhibiting drug-efflux pumps involved in drug resistance, modulating the tumor microenvironment and immune system, and applying drug combination therapy using nanomedicine.

show abstract

Intracellular autofluorescence: a biomarker for epithelial cancer stem cells

Cited by 173 publications

References 35 publications

Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms

Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms

The role of steroid hormones in breast cancer stem cells

Therapeutic strategies for targeting cancer stem cells

Contact Info

Product

Resources

About