Invading Basement Membrane Matrix Is Sufficient for MDA-MB-231 Breast Cancer Cells to Develop a Stable In Vivo Metastatic Phenotype

Abdelkarim, Mohamed; Vintonenko, Nadejda; Starzec, Anna; Robles, Aniela; Aubert, Julie; Martin, Marie-Laure; Mourah, Samia; Podgorniak, Marie-Pierre; Rodrigues-Ferreira, Sylvie; Nahmias, Clara; Couraud, Pierre‐Olivier; Doliger, Christelle; Sainte-Cathérine, Odile; Peyri, N; Chen, Lei; Mariau, Jérémie; Etienne, Monique; Perret, Gérard-Yves; Crépin, Michel; Poyet, Jean-Luc; Khatib, Abdel‐Majid; Benedetto, Mélanie Di

doi:10.1371/journal.pone.0023334

Cited by 24 publications

(24 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the MFP and SC tumour models, the basement membrane was thickened compared to healthy liver blood vessels (Figure 3B). This observation is consistent with the xenografted MDA-MB-231-H2N cell line being poorly invasive like its parental line, MDA-MB-231 [33]. Conversely, a more metastatic cell line is often capable of using MMPs to degrade the basement membrane to enable cell migration through neighbouring blood vessels [33].…”

Section: Resultssupporting

confidence: 72%

Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

Poon²,

Owen

et al. 2012

BMC Cancer

View full text Add to dashboard Cite

BackgroundHuman tumour xenografts in immune compromised mice are widely used as cancer models because they are easy to reproduce and simple to use in a variety of pre-clinical assessments. Developments in nanomedicine have led to the use of tumour xenografts in testing nanoscale delivery devices, such as nanoparticles and polymer-drug conjugates, for targeting and efficacy via the enhanced permeability and retention (EPR) effect. For these results to be meaningful, the hyperpermeable vasculature and reduced lymphatic drainage associated with tumour pathophysiology must be replicated in the model. In pre-clinical breast cancer xenograft models, cells are commonly introduced via injection either orthotopically (mammary fat pad, MFP) or ectopically (subcutaneous, SC), and the organ environment experienced by the tumour cells has been shown to influence their behaviour.MethodsTo evaluate xenograft models of breast cancer in the context of EPR, both orthotopic MFP and ectopic SC injections of MDA-MB-231-H2N cells were given to NOD scid gamma (NSG) mice. Animals with matched tumours in two size categories were tested by injection of a high molecular weight dextran as a model nanocarrier. Tumours were collected and sectioned to assess dextran accumulation compared to liver tissue as a positive control. To understand the cellular basis of these observations, tumour sections were also immunostained for endothelial cells, basement membranes, pericytes, and lymphatic vessels.ResultsSC tumours required longer development times to become size matched to MFP tumours, and also presented wide size variability and ulcerated skin lesions 6 weeks after cell injection. The 3 week MFP tumour model demonstrated greater dextran accumulation than the size matched 5 week SC tumour model (for P < 0.10). Immunostaining revealed greater vascular density and thinner basement membranes in the MFP tumour model 3 weeks after cell injection. Both the MFP and SC tumours showed evidence of insufficient lymphatic drainage, as many fluid-filled and collagen IV-lined spaces were observed, which likely contain excess interstitial fluid.ConclusionsDextran accumulation and immunostaining results suggest that small MFP tumours best replicate the vascular permeability required to observe the EPR effect in vivo. A more predictable growth profile and the absence of ulcerated skin lesions further point to the MFP model as a strong choice for long term treatment studies that initiate after a target tumour size has been reached.

show abstract

Section: Resultssupporting

confidence: 72%

Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

Poon²,

Owen

et al. 2012

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Examination of ATIP3 levels in breast tumors may contribute to identify a population of patients at high risk of fatal complication, who should be the subject of careful medical follow-up. Using a bioluminescence-based experimental mouse model for cancer metastasis (23,25,26), we showed that restoring ATIP3 expression into highly metastatic ATIP3-deficient D3H2LN breast tumor cells significantly delays the time-course of metastasis and reduces the number of detectable metastases per mouse at all times examined. ATIP3 expression in cancer cells also strongly reduces the size of metastatic foci as well as the number of mice fully invaded with large metastases.…”

Section: Discussionmentioning

confidence: 98%

“…Experimental metastasis was conducted as described (23,25,26) following intracardiac injection of stable ATIP3-negative [WT (wild-type), GFP] or positive (Cl3, Cl6) D3H2LN cell clones. All injected cells showed similar viability as measured by Annexin V apoptosis kit (Beckman Coulter).…”

Section: Intracardiac Experimental Mouse Model Of Metastasismentioning

confidence: 99%

“…In vivo effects of ATIP3 on the metastatic potential of breast cancer cells were evaluated using a well-defined experimental mouse model of metastasis monitored by intravital bioluminescence imaging (23,25,26). Highly metastatic, ATIP3-negative, D3H2LN breast cancer cells were transfected with either GFP or GFP-ATIP3, and independent stable cell clones (Cl3 and Cl6) expressing moderate levels of ATIP3 were selected ( Fig.…”

Section: Atip3 Limits Breast Cancer Metastatic Colonization In Vivomentioning

confidence: 99%

See 1 more Smart Citation

ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

et al. 2013

Self Cite

View full text Add to dashboard Cite

Metastasis, a fatal complication of breast cancer, does not fully benefit from available therapies. In this study, we investigated whether ATIP3, the major product of 8p22 MTUS1 gene, may be a novel biomarker and therapeutic target for metastatic breast tumors. We show that ATIP3 is a prognostic marker for overall survival among patients with breast cancer. Notably, among metastatic tumors, low ATIP3 levels associate with decreased survival of the patients. By using a well-defined experimental mouse model of cancer metastasis, we show that ATIP3 expression delays the time-course of metastatic progression and limits the number and size of metastases in vivo. In functional studies, ATIP3 silencing increases breast cancer cell migration, whereas ATIP3 expression significantly reduces cell motility and directionality. We report here that ATIP3 is a potent microtubule-stabilizing protein whose depletion increases microtubule dynamics. Our data support the notion that by decreasing microtubule dynamics, ATIP3 controls the ability of microtubule tips to reach the cell cortex during migration, a mechanism that may account for reduced cancer cell motility and metastasis. Of interest, we identify a functional ATIP3 domain that associates with microtubules and recapitulates the effects of ATIP3 on microtubule dynamics, cell proliferation, and migration. Our study is a major step toward the development of new personalized treatments against metastatic breast tumors that have lost ATIP3 expression. Cancer Res; 73(9); 2905-15. Ó2013 AACR.

show abstract

“…MDA-MB-231 cells behave aggressively in culture and murine models, displaying a metastatic phenotype that suggests that these cells retain the protein expression profile which allowed them to metastasize through the basement membrane of the original patient (41). …”

Section: Introductionmentioning

confidence: 99%

Galectin-3 Binding Protein Secreted by Breast Cancer Cells Inhibits Monocyte-Derived Fibrocyte Differentiation

White

Roife

Gomer

2015

The Journal of Immunology

View full text Add to dashboard Cite

To metastasize, tumor cells often need to migrate through a layer of collagen-containing scar tissue which encapsulates the tumor. A key component of scar tissue and fibrosing diseases is the monocyte-derived fibrocyte, a collagen-secreting pro-fibrotic cell. To test the hypothesis that invasive tumor cells may block the formation of the fibrous sheath, we determined if tumor cells secrete factors that inhibit monocyte-derived fibrocyte differentiation. We found that the human metastatic breast cancer cell line MDA-MB 231 secretes activity that inhibits human monocyte-derived fibrocyte differentiation, while less aggressive breast cancer cell lines secrete less of this activity. Purification indicated that Galectin-3 Binding Protein (LGALS3BP) is the active factor. Recombinant LGALS3BP inhibits monocyte-derived fibrocyte differentiation, and immunodepletion of LGALS3BP from MDA-MB 231 conditioned media removes the monocyte-derived fibrocyte differentiation-inhibiting activity. LGALS3BP inhibits the differentiation of monocyte-derived fibrocytes from wild-type mouse spleen cells, but not from SIGN-R1−/− mouse spleen cells, suggesting that CD209/SIGN-R1 is required for the LGALS3BP effect. Galectin-3 and galectin-1, binding partners of LGALS3BP, potentiate monocyte-derived fibrocyte differentiation. In breast cancer biopsies, increased levels of tumor cell-associated LGALS3BP were observed in regions of the tumor that were invading the surrounding stroma. These findings suggest LGALS3BP and galectin-3 as new targets to treat metastatic cancer and fibrosing diseases.

show abstract

Invading Basement Membrane Matrix Is Sufficient for MDA-MB-231 Breast Cancer Cells to Develop a Stable In Vivo Metastatic Phenotype

Cited by 24 publications

References 43 publications

Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

Blood vessel hyperpermeability and pathophysiology in human tumour xenograft models of breast cancer: a comparison of ectopic and orthotopic tumours

ATIP3, a Novel Prognostic Marker of Breast Cancer Patient Survival, Limits Cancer Cell Migration and Slows Metastatic Progression by Regulating Microtubule Dynamics

Galectin-3 Binding Protein Secreted by Breast Cancer Cells Inhibits Monocyte-Derived Fibrocyte Differentiation

Contact Info

Product

Resources

About