Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion

Valentinis, Barbara; Morrione, Andrea; Peruzzi, Francesca; Prisco, Marco di; Reiss, Krzysztof; Baserga, Renato

doi:10.1038/sj.onc.1202471

Cited by 85 publications

(66 citation statements)

References 57 publications

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“…For such cells to survive in suspension, as required for circulating tumour cells to be transported in the blood stream or lymphatics and progress to forming tumour metastasis, these cells must evade a form of apoptosis termed anoikis. [26][27][28] Here, using standard methods, 29,30 we attempted to mimic this situation in vitro by coating tissue culture plates with p-HEMA and thus inhibiting the ability of the cells to attach to the tissue culture plastic. We subse- quently assessed the ability of the cells to survive i.e.…”

Section: Exosomes Confer Anoikis Sensitivity/resistance To Secondary mentioning

confidence: 99%

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

O’Brien

Rani

Corcoran

et al. 2013

European Journal of Cancer

203

161

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Background: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i) 8 variant, as well as exosomes from TNBC patient sera compared to normal sera. Methods: Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i) 8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/ recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays. Results: Hs578Ts(i) 8 -exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i) 8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i) 8 -exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i) 8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i) 8 -exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our 0959-8049/$ -see front matter Ó

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Section: Exosomes Confer Anoikis Sensitivity/resistance To Secondary mentioning

confidence: 99%

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

O’Brien

Rani

Corcoran

et al. 2013

European Journal of Cancer

203

161

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“…The protocol described in our previous work was followed (Valentinis et al, 1998(Valentinis et al, , 1999a. Evaluation of size and number of aggregates was done under the inverted phasecontrast microscope.…”

Section: Aggregation Assaymentioning

confidence: 99%

“…500 mg of total protein lysates were immunoprecipitated with anti-phosphotyrosine (PY20 ± Transduction Laboratories), and agarose-conjugated antimouse IgG (Sigma) antibodies. PI3-kinase activity associated with PY was determined according to previously described protocol (Valentinis et al, 1999a).…”

Section: Pi3-kinase Assaymentioning

confidence: 99%

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

et al. 2000

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LNCaP prostatic cancer cells are characterized by having a PTEN mutation, low levels of type 1 insulinlike growth factor receptor (IGF-IR) and no IRS-1, one of the major substrates of the IGF-IR. The absence of IRS-1, an activator of PI3-kinase, is compensated in these cells by the mutation in PTEN, an inhibitor of PI3-kinase. However, IGF-IR signaling in the absence of IRS-1 can cause cell di erentiation and growth arrest. We hypothesized that these three characteristics may not be unrelated, speci®cally that, together, they may favor the metastatic spread of prostatic cancer cells without decreasing their growth potential. In support of this hypothesis, we report here that: (1) IRS-1 expression increases cell adhesion and decreases cell motility; (2) over-expression of the IGF-IR, in the absence of IRS-1, causes growth arrest and (3) a combination of IGF-IR and IRS-1 restores the transformed phenotype of LNCaP cells. These ®ndings suggest a mechanism by which prostatic cancer cells can achieve metastatic potential without interfering with their growth potential.

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“…Such nonspecific degradation of the extracel lular matrix undoubtedly causes detachment of my oblasts (and other cell types), which in turn could result in cell death. Anoikis is a specific form of apoptotic cell death that results from the disruption of cell-matrix interactions (16,63), although the signaling mechanisms involved in this process are still unclear (17,18,40,68,69). Pancreatic islet cells transduced with an anoikis-inhibiting molecule showed enhanced viability in vitro, and transplantation of these cells (for the treatment of insu lin-dependent diabetes) resulted in improved pancreatic function in vivo (65).…”

Section: Effects Of Proteolytic Enzymesmentioning

confidence: 99%

Exposure to Tissue Culture Conditions Can Adversely Affect Myoblast Behavior in Vivo in Whole Muscle Grafts: Implications for Myoblast Transfer Therapy

Smythe

Grounds

2000

Cell Transplant

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The effects of tissue culture conditions on the viability of myoblasts in whole muscles transplanted in vivo were investigated. Whole male (SJL/J) donor muscles were exposed to various tissue culture reagents and proteolytic enzymes, and allografted into female (SJL/J) host mice. Desmin immunohistochemistry was used to assess the numbers of myogenic cells (as an index of myoblast viability and the extent of regeneration) in tissue sections of whole-muscle grafts sampled on days 7 and 14. DNA quantitation with a Y-chromosome-specific probe was used to determine the total Y-l sequence DNA (as an index of myoblast survival and proliferation) in whole-muscle grafts sampled on days 1, 3, and 7. In grafts exposed to serum-free medium, there was a delay in myoblast fusion at 7 days that was recovered by 14 days, but exposure to serum (10% or 20%) had a prolonged adverse effect on myotube formation at 14 days. DNA quantitation demonstrated that either serum-free culture medium or 10% serum enhanced the number of male cells within whole-muscle grafts at 7 days. Proteolytic digestion (even for 5 min) of whole muscles prior to grafting was extremely detrimental to myoblast survival and viability at 7 and 14 days. The unexpected finding of adverse effects of tissue culture conditions on the regeneration of whole-muscle grafts in vivo appears to parallel the major problem of the rapid death of isolated cultured donor myoblasts after injection in myoblast transfer therapy. The use of whole-muscle grafts provides an alternative and sensitive model to analyze the crucial effects of various tissue culture components on the subsequent survival and proliferation of myogenic cells in vivo.

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Anti-apoptotic signaling of the IGF-I receptor in fibroblasts following loss of matrix adhesion

Cited by 85 publications

References 57 publications

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

IGF-I receptor signaling in a prostatic cancer cell line with a PTEN mutation

Exposure to Tissue Culture Conditions Can Adversely Affect Myoblast Behavior in Vivo in Whole Muscle Grafts: Implications for Myoblast Transfer Therapy

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