Collective cell migration in morphogenesis and cancer

Friedl, Peter; Hegerfeldt, Yael; Tusch, Miriam

doi:10.1387/ijdb.041821pf

Cited by 401 publications

(290 citation statements)

References 67 publications

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“…b1 integrin is a well established player in cell motility (Friedl et al, 2004;Cordes and Park, 2007;Caswell et al, 2009;Friedl and Wolf, 2010). In this study, we show that its silencing, as well its inhibition, affects the invasive properties of A549 cells, both in terms of directional migration through Transwells and b1 integrin controls EGFR signaling V Morello et al in the ability to invade into 3D matrix.…”

Section: Discussionmentioning

confidence: 51%

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

et al. 2011

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Lung cancer is the leading cause of cancer death worldwide. The epidermal growth factor receptor (EGFR) represents the main target for non-small cell lung cancer (NSCLC) therapy, as its overexpression or constitutive activation contributes to malignancy and correlates with poor prognosis. Our previous work demonstrated that in epithelial cells b1 integrin is required for propagating EGFR signaling from the plasma membrane to the nucleus. In this study, we silenced b1 integrin in human NSCLC A549 cells. The b1 integrin-silenced cells show a defective activation of the EGFR signaling cascade, leading to decreased in vitro proliferation, enhanced sensitivity to cisplatin and Gefitinib, impaired migration and invasive behavior. Inhibitory effects on tumor growth and on the EGFR pathway were also observed in in vivo experiments. Moreover, b1 integrin silencing increases the amount of EGFR on the cell surface, suggesting that b1 integrin is required for efficient constitutive EGFR turnover at the cell membrane. Although the rate of EGF internalization and recycling is not affected in silenced cells, EGFR signaling is recovered only by expression of the Rab-coupling protein RCP, indicating that b1 integrin sustains the endocytic machinery required for EGFR signaling. Overall, these results show that b1 integrin is an essential regulator of EGFR signaling and tumorigenic properties of lung cancer cells, and that its silencing might represent an adjuvant approach to anti-EGFR therapy.

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Section: Discussionmentioning

confidence: 51%

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

et al. 2011

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“…This approach is expected to improve current cancer modeling efforts because a multiscale approach model connects previous work focused on specific scales and specific processes (e.g., single cell motion) by performing 3-dimensional simulations of in vivo tumors. This methodology further allows the possibility to see beyond the current reductionist picture of invasion and migration [78,111,187,198,204,117,206,64,179,75,77,53,172], with the goal to enable prediction of disease progression and treatment response based on patient-specific tumor characteristics. …”

Section: Resultsmentioning

confidence: 99%

Nonlinear Modeling and Simulation of Tumor Growth

Cristini

Frieboes

et al. 2008

Selected Topics in Cancer Modeling

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“…Bar 50 m muscle strands and lymphatic vascular tracks. Collective invasion is considered as predominant invasion pattern in several human cancer types, including sarcoma, epithelial cancer and melanoma (Christiansen and Rajasekaran 2006;Friedl et al 2004Friedl et al , 1995Gaggioli et al 2007;Hegerfeldt et al 2002), yet its molecular control mechanisms and relevance for distant metastasis remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Dynamic imaging of cancer growth and invasion: a modified skin-fold chamber model

Alexander

Koehl²,

Hirschberg

et al. 2008

Histochem Cell Biol

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222

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The metastatic invasion of cancer cells from the primary lesion into the adjacent stroma is a key step in cancer progression, and is associated with poor outcome. The principles of cancer invasion have been experimentally addressed in various in vitro models; however, key steps and mechanisms in vivo remain unclear. Here, we establish a modiWed skin-fold chamber model for orthotopic implantation, growth and invasion of human HT-1080 Wbrosarcoma cells, dynamically reconstructed by epiXuorescence and multiphoton microscopy. This strategy allows repeated imaging of tumor growth, tumor-induced angiogenesis and invasion, as either individual cells, or collective strands and cell masses that move along collagen-rich extracellular matrix and coopt host tissue including striated muscle strands and lymph vessels. This modiWed window model will be suited to address mechanisms of cancer invasion and metastasis, and related experimental therapy.

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Collective cell migration in morphogenesis and cancer

Cited by 401 publications

References 67 publications

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

β1 integrin controls EGFR signaling and tumorigenic properties of lung cancer cells

Nonlinear Modeling and Simulation of Tumor Growth

Dynamic imaging of cancer growth and invasion: a modified skin-fold chamber model

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