Hypoxia promotes invasion and metastasis of breast cancer cells by increasing lysyl oxidase expression

Erler, J.T.; Jeffrey, Stefanie S.; Aj, Giaccia

doi:10.1186/bcr1186

Cited by 2 publications

(2 citation statements)

References 2 publications

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“…We considered that the main reason for the different features between the ductal and solid cancer cell aggregates was the more hypoxic microenvironment inside the latter, than the former (figure 2(a)). A hypoxic environment increases EMT marker expression, invasion activity, and the drug resistance of cancer cells [35,36]. Our findings were similar to those of Singh et al [18] who showed that a hypoxic microenvironment in cell spheroids changed the migratory behavior of cancer cells towards an aggressive propensity.…”

Section: Discussionsupporting

confidence: 91%

In vitro breast cancer model with patient-specific morphological features for personalized medicine

Han¹,

Jeon²,

Kim³

et al. 2022

Biofabrication

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In vitro cancer models that can simulate patient-specific drug responses for personalized medicine have attracted significant attention. However, the technologies used to produce such models can only recapitulate the morphological heterogeneity of human cancer tissue. Here, we developed a novel 3D technique to bioprint an in vitro breast cancer model with patient-specific morphological features. This model can precisely mimic the cellular microstructures of heterogeneous cancer tissues and produce drug responses similar to those of human cancers. We established a bioprinting process for generating cancer cell aggregates with ductal and solid tissue microstructures that reflected the morphology of breast cancer tissues, and applied it to develop breast cancer models. The genotypic and phenotypic characteristics of the ductal and solid cancer aggregates bioprinted with human breast cancer cells (MCF7, SKBR3, MDA-MB-231) were respectively similar to those of early and advanced cancers. The bioprinted solid cancer cell aggregates showed significantly higher hypoxia (>8 times) and mesenchymal (>2-4 times) marker expressions, invasion activity (>15 times), and drug resistance than the bioprinted ductal aggregates. Co-printing the ductal and solid aggregates produced heterogeneous breast cancer tissue models that recapitulated three different stages of breast cancer tissue morphology. The bioprinted cancer tissue models representing advanced cancer were more and less resistant, respectively, to the anthracycline antibiotic doxorubicin and the hypoxia-activated prodrug tirapazamine; these were analogous to the results in human cancer. The present findings showed that cancer cell aggregates can mimic the pathological micromorphology of human breast cancer tissue and they can be bioprinted to produce breast cancer tissue in vitro that can morphologically represent the clinical stage of cancer in individual patients.

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Section: Discussionsupporting

confidence: 91%

In vitro breast cancer model with patient-specific morphological features for personalized medicine

Han¹,

Jeon²,

Kim³

et al. 2022

Biofabrication

View full text Add to dashboard Cite

show abstract

“…Also, it has long been hypothesized in the field that metastatic cells need a certain degree of flexibility and deformability to escape their original niche [40][41][42] . By analysing metastatic lesions in lungs from MMTV-PyMT mice we now provide the first evidence that supports this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

The nanomechanical signature of breast cancer

et al. 2012

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Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance.

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Hypoxia promotes invasion and metastasis of breast cancer cells by increasing lysyl oxidase expression

Cited by 2 publications

References 2 publications

In vitro breast cancer model with patient-specific morphological features for personalized medicine

In vitro breast cancer model with patient-specific morphological features for personalized medicine

The nanomechanical signature of breast cancer

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