Understanding Breast Cancer Aggressiveness and Its Implications in Diagnosis and Treatment

Afifi, Nader; Barrero, Carlos

doi:10.3390/jcm12041375

Cited by 13 publications

(12 citation statements)

References 17 publications

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“…Currently, the determination of breast tumor aggressiveness relies on the assessment of the stage and molecular subtype which influence the prognosis, risks of recurrence and mortality, and treatment options [ 42 ]. Nonetheless, up to 20% of breast cancer cases, especially the aggressive TNBC subtype, will relapse and potentially evolve in metastatic disease and death [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Targeting cholesterol impairs cell invasion of all breast cancer types

Maja,

Verfaillie,

Van Der Smissen

et al. 2024

Cancer Cell Int

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Background Breast cancer clinical outcome relies on its intrinsic molecular subtype and mortality is almost exclusively due to metastasis, whose mechanism remains unclear. We recently revealed the specific contribution of plasma membrane cholesterol to the invasion of malignant MCF10CAIa but not premalignant MCF10AT and normal MCF10A cell lines in 2D, through invadopodia formation and extracellular matrix (ECM) degradation. In the present study, we address the impact of breast cancer subtypes, mutations and aggressiveness on cholesterol implication in breast cancer cell invasion and 3D spheroid invasion and growth. Methods We used nine breast cancer cell lines grouped in four subtypes matching breast tumor classification. Four of these cell lines were also used to generate 3D spheroids. These cell lines were compared for cell invasion in 2D and 3D, spheroid growth in 3D, gelatin degradation, cortactin expression, activation and subcellular distribution as well as cell surface cholesterol distribution and lipid droplets. The effect of plasma membrane cholesterol depletion on all these parameters was determined in parallel and systematically compared with the impact of global matrix metalloproteinase (MMP) inhibition. Results The six invasive cell lines in 2D were sensitive to partial cholesterol depletion, independently of their subtype, aggressiveness or mutation. Nevertheless, the effect was stronger in the three cell lines able to degrade gelatin. 3D spheroid invasion was also reduced after cholesterol depletion in all breast cancer subtypes tested. Notably, targeting cholesterol was more powerful than MMP inhibition in reducing invasion in both 2D and 3D culture models. Moreover, cholesterol depletion in the six invasive cell lines impaired cortactin distribution in the perinuclear region where invadopodia localized. Breast cancer cell line aggressiveness relied on cholesterol-enriched domains at the ECM-free side and intracellular lipid droplets. Furthermore, the three gelatin-degrading cell lines were characterized by increased cholesterol-enriched submicrometric domains at their ECM-contact side. Conclusion Together, our data suggest cell surface cholesterol combined with lipid droplet labeling as a breast cancer cell aggressiveness marker. They also open the way to test other cholesterol-targeting drugs in more complex models to further evaluate whether cholesterol could represent a strategy in breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Targeting cholesterol impairs cell invasion of all breast cancer types

Maja,

Verfaillie,

Van Der Smissen

et al. 2024

Cancer Cell Int

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show abstract

“…MDA-MB-231 is triple-negative for ER/PR and HER2 and also exhibits loss of E-cadherin expression, indicating a very high-aggressive phenotype. 31 Classified tumor cell lines can aid in identifying unknown tumor cells based on unique characteristics, contributing to tumor heterogeneity investigation.…”

Section: Classification Of Breast Tumor Cell Linesmentioning

confidence: 99%

“…In contrast, SK-BR-3, which is double-negative for ER/PR and experiences loss of E-cadherin expression, demonstrates a partial transition toward a high-aggressive phenotype. MDA-MB-231 is triple-negative for ER/PR and HER2 and also exhibits loss of E-cadherin expression, indicating a very high-aggressive phenotype . Classified tumor cell lines can aid in identifying unknown tumor cells based on unique characteristics, contributing to tumor heterogeneity investigation.…”

Section: Theorymentioning

confidence: 99%

Formation Pattern Analysis of Spheroids Formed by a Droplet-Based Microfluidic System for Predicting the Aggressiveness of Tumor Cells

Lee,

Woo,

Jung

et al. 2024

ACS Biomater. Sci. Eng.

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Examining tumor heterogeneity is essential for selecting an appropriate anticancer treatment for an individual. This study aimed to distinguish low-and highaggressive tumor cells by analyzing the formation patterns of spheroids. The droplet-based microfluidic system was employed for the formation of each spheroid from four different subtypes of breast tumor cells. Additionally, heterotypic spheroids with T lymphocytes and cancer-associated fibroblasts (CAFs) were produced, and distinctions between low-and high-aggressive tumor cells were explored through the analysis of formation patterns using circularity, convexity, and cell distributions. In both homotypic spheroids and heterotypic spheroids with T lymphocytes, spheroids formed from low-aggressive tumor cells exhibited high circularity and convexity. On the other hand, spheroids formed from high-aggressive tumor cells had relatively low circularity and convexity. In the case of heterotypic spheroids with CAFs, circularity and convexity did not exhibit clear differences between low-and high-aggressive tumor cells, but distinct variations were observed in cell distributions. CAFs and low-aggressive tumor cells were evenly distributed, whereas the CAFs were predominantly located in the inner layer, and highaggressive tumor cells were primarily located in the outer layer. This finding can offer valuable insights into predicting the aggressiveness of unknown tumor cells.

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“…Breast cancer is a complex and heterogeneous disease that poses many challenges for research and treatment. Some of these challenges are to determine cancer subtypes, to understand the aggressiveness of cancer [ 28 ], neoadjuvant treatment response [ 29 ], or why most breast cancer patients do not respond to immunotherapy [ 30 ]. Another area of research is to develop predictive biomarkers for personalized medicine in breast cancer [ 31 , 32 ].…”

Section: Breast Cancer Therapies and Open Research Questionsmentioning

confidence: 99%

The Revolution in Breast Cancer Diagnostics: From Visual Inspection of Histopathology Slides to Using Desktop Tissue Analysers for Automated Nanomechanical Profiling of Tumours

Stolz

2024

Bioengineering

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We aim to develop new portable desktop tissue analysers (DTAs) to provide fast, low-cost, and precise test results for fast nanomechanical profiling of tumours. This paper will explain the reasoning for choosing indentation-type atomic force microscopy (IT-AFM) to reveal the functional details of cancer. Determining the subtype, cancer stage, and prognosis will be possible, which aids in choosing the best treatment. DTAs are based on fast IT-AFM at the size of a small box that can be made for a low budget compared to other clinical imaging tools. The DTAs can work in remote areas and all parts of the world. There are a number of direct benefits: First, it is no longer needed to wait a week for the pathology report as the test will only take 10 min. Second, it avoids the complicated steps of making histopathology slides and saves costs of labour. Third, computers and robots are more consistent, more reliable, and more economical than human workers which may result in fewer diagnostic errors. Fourth, the IT-AFM analysis is capable of distinguishing between various cancer subtypes. Fifth, the IT-AFM analysis could reveal new insights about why immunotherapy fails. Sixth, IT-AFM may provide new insights into the neoadjuvant treatment response. Seventh, the healthcare system saves money by reducing diagnostic backlogs. Eighth, the results are stored on a central server and can be accessed to develop strategies to prevent cancer. To bring the IT-AFM technology from the bench to the operation theatre, a fast IT-AFM sensor needs to be developed and integrated into the DTAs.

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Understanding Breast Cancer Aggressiveness and Its Implications in Diagnosis and Treatment

Abstract: Breast cancer (BC) is the most common form of cancer in women worldwide [...]

Cited by 13 publications

References 17 publications

Targeting cholesterol impairs cell invasion of all breast cancer types

Targeting cholesterol impairs cell invasion of all breast cancer types

Formation Pattern Analysis of Spheroids Formed by a Droplet-Based Microfluidic System for Predicting the Aggressiveness of Tumor Cells

The Revolution in Breast Cancer Diagnostics: From Visual Inspection of Histopathology Slides to Using Desktop Tissue Analysers for Automated Nanomechanical Profiling of Tumours

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