The invasion mode of GH3 cells is conditioned by collagen subtype, and its efficiency depends on cell–cell adhesion

Azorin, E; Solano-Agama, Carmen; Mendoza-Garrido, M. Eugenia

doi:10.1016/j.abb.2012.08.011

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…Cell morphology parameters, EMT markers, and actin changes were more pronounced in GH3- Aip -KD cells, supporting the results on increased migration since in order for cells to invade through the extracellular matrix, filopodia/actin spikes protrude, which are crucial for successful migration/invasion. Media from macrophages stimulated GH3- Aip -KD cells to increase migration and invasion, while this cell type typically grown in complete medium do not show changes in migration/invasion assays [56, 57].…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

Barry

Carlsen²,

Marques

et al. 2019

Oncogene

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The molecular mechanisms leading to aryl hydrocarbon receptor interacting protein (AIP) mutation-induced aggressive, young-onset growth hormone-secreting pituitary tumors are not fully understood. In this study, we have identified that AIP-mutation-positive tumors are infiltrated by a large number of macrophages compared to sporadic tumors. Tissue from pituitary-specific Aip-knockout (AipFlox/Flox;Hesx1Cre/+) mice recapitulated this phenotype. Our human pituitary tumor transcriptome data revealed the “epithelial-to-mesenchymal transition (EMT) pathway” as one of the most significantly altered pathways in AIPpos tumors. Our in vitro data suggest that bone marrow-derived macrophage-conditioned media induces more prominent EMT-like phenotype and enhanced migratory and invasive properties in Aip-knockdown somatomammotroph cells compared to non-targeting controls. We identified that tumor-derived cytokine CCL5 is upregulated in AIP-mutation-positive human adenomas. Aip-knockdown GH3 cell-conditioned media increases macrophage migration, which is inhibited by the CCL5/CCR5 antagonist maraviroc. Our results suggest that a crosstalk between the tumor and its microenvironment plays a key role in the invasive nature of AIP-mutation-positive tumors and the CCL5/CCR5 pathway is a novel potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

Barry

Carlsen²,

Marques

et al. 2019

Oncogene

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“…TAT/CLV‐Dox MM induced the highest decrease in cell migration and also inhibited the mesenchymal‐amoeboid transition observed in PBS and CLV‐Dox groups (videos not shown). The transition between cellular motility shapes is a key factor to help cancer cells to migrate and invade healthy tissues …”

Section: Resultsmentioning

confidence: 99%

“…The 3D imaging plug‐in was used to create a volume rendering of the cellular motion over time of analysis (Figure c). The brightness threshold was adjusted to view all cells within the imaging area or only the thicker cells, a feature that allows identification of mitosis, apoptosis, and transition between mesenchymal and amoeboid cellular morphologies …”

Section: Methodsmentioning

confidence: 99%

Mixed Nanosized Polymeric Micelles as Promoter of Doxorubicin and miRNA‐34a Co‐Delivery Triggered by Dual Stimuli in Tumor Tissue

Salzano

Costa

Sarısözen

et al. 2016

Small

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Dual stimuli-sensitive mixed polymeric micelles (MM) are developed for co-delivery of the endogenous tumor suppressor miRNA-34a and the chemotherapeutic agent doxorubicin (Dox) into cancer cells. The novelty of the system resides in two stimuli-sensitive prodrugs, a matrix metalloproteinase 2 (MMP2)-sensitive Dox conjugate and a reducing agent (glutathione, GSH)-sensitive miRNA-34a conjugate, self-assembled in a single particle decorated with a polyethylene glycol corona for longevity and a cell-penetrating peptide (TATp) for enhanced intracellular delivery. The MMP2-sensitivity of the system results in 3-fold higher cytotoxicity in MMP2-overexpressing HT1080 cells compared to low MMP2-expressing MCF7 cells. Cellular internalization of Dox increases by more than 70% after inclusion of TATp to the formulation. MMP2-sensitive MM also inhibits proliferation and migration of HT1080 cells. Moreover, GSH-sensitive MM allows for an efficient downregulation of Bcl2, survivin, and notch1 (65%, 55% and 46%, respectively) in HT1080 cells. Combination of both conjugates in dual sensitive MM reduces HT1080 cell viability to 40% and expression of Bcl2 and survivin. Finally, 50% cell death is observed in 3D models of tumor mass. The results confirm the potential of the MM to co-deliver miRNA-34a and doxorubicin triggered by dual stimuli inherent of tumor tissues.

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“…Moreover, a greater range of integrin subunits was observed in the stroma of tumors (α 1 , α 3 , α 5 , α 6 , α ν , β 1 , β 3 , β 4 , β 5 ) compared to the connective tissue found in the normal pituitary (α 1 , α 5 , β 1 ) [95], and the expression of the integrin-β1 subunit correlated with pituitary tumor invasiveness [99]. Finally, the exposure of GH3 cells to different collagen subtypes has been shown to differently affect their invasion ability and migration strategy in vitro, highlighting the functional complexity that ECM composition may have in pituitary tumors [100].…”

Section: Composition and Remodeling Of The Extracellular Matrix Inmentioning

confidence: 99%

The Microenvironment of Pituitary Tumors—Biological and Therapeutic Implications

Ilie

Vasiljevic

Raverot

et al. 2019

Cancers

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The tumor microenvironment (TME) includes resident and infiltrative non-tumor cells, as well as blood and lymph vessels, extracellular matrix molecules, and numerous soluble factors, such as cytokines and chemokines. While the TME is now considered to be a prognostic tool and a therapeutic target for many cancers, little is known about its composition in pituitary tumors. This review summarizes our current knowledge of the TME within pituitary tumors and the strong interest in TME as a therapeutic target. While we cover the importance of angiogenesis and immune infiltrating cells, we also address the role of the elusive folliculostellate cells, the emerging literature on pituitary tumor-associated fibroblasts, and the contribution of extracellular matrix components in these tumors. The cases of human pituitary tumors treated with TME-targeting therapies are reviewed and emerging concepts of vascular normalization and combined therapies are presented. Together, this snapshot overview of the current literature pinpoints not only the underestimated role of TME components in pituitary tumor biology, but also the major promise it may offer for both prognosis and targeted therapeutics.

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The invasion mode of GH3 cells is conditioned by collagen subtype, and its efficiency depends on cell–cell adhesion

Cited by 8 publications

References 39 publications

Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors

Mixed Nanosized Polymeric Micelles as Promoter of Doxorubicin and miRNA‐34a Co‐Delivery Triggered by Dual Stimuli in Tumor Tissue

The Microenvironment of Pituitary Tumors—Biological and Therapeutic Implications

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