Stem cell protection mechanisms in planarians: the role of some heat shock genes

Isolani, Maria-Emilia; Conte, Maria; Deri, Paolo; Batistoni, Renata

doi:10.1387/ijdb.113432mi

Cited by 13 publications

(12 citation statements)

References 44 publications

(56 reference statements)

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“…IPA analysis showed that endoplasmic reticulum stress was significantly changed at the very early phase of newt limb regeneration, suggesting cell stress response is induced by amputation. Heat shock proteins play crucial roles in the modulation of pathways regulating stem cell activity, regeneration and tissue repair (Isolani et al, 2012). The up-regulation of molecular chaperone HSP90B1 and heat shock proteins HSPA5 and HSPA9 were observed in our study, being consistent with the findings that the level of chaperone genes was increased in the regenerating newt and axolotl limbs (Levesque et al, 2005, Monaghan et al, 2009, Xenopus laevis hindlimbs (Pearl et al, 2008).…”

Section: Immune Response and Cell Deathsupporting

confidence: 92%

iTRAQ-based proteomic analysis of adaptive response in the regenerating limb of the Cynops orientalis newt

Geng¹,

Guo²,

Zang³

et al. 2015

Int. J. Dev. Biol.

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The newt has the powerful capacity to regenerate lost limbs following amputation, and represents an excellent model organism to study regenerative processes. However, the molecular basis of the adaptive response in the regenerating limb of the Chinese fire-bellied newt Cynops orientalis immediately after amputation remains unclear. To better understand the adaptive response immediately after limb amputation at the protein level, we used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS methods to analyze changes in the proteome of the regenerating newt limb that occurred 2 h and 8 h after amputation. We identified 152 proteins with more than 1.5-fold change in expression compared to control. GO annotation analysis classified these proteins into several categories such as signaling, Ca 2+ binding and translocation, transcription and translation, immune response, cell death, cytoskeleton, metabolism, etc. Further ingenuity pathway analysis (IPA) showed that several signaling pathways were significantly changed at 2 h and 8 h after amputation, including EIF2 signaling, acute phase response signaling, tight junction signaling and calcium signaling, suggesting these pathways may be closely related to the adaptive response immediately after limb amputation. This work provides novel insights into understanding the molecular processes related to newt limb regeneration immediately after amputation, and a basis for further study of regenerative medicine. KEY WORDS: Cynops orientalis, limb regeneration, proteomic, stress response, cell deathAmong vertebrates, urodele salamanders possess remarkable capability to regenerate appendages from any level of amputation through blastema formation. Subsequently, blastema cells that morphologically resemble mesenchymal stem-like cells self-organize into the amputated limb parts , Nye et al., 2003. Adult newt has already been used as an important model for the limb regeneration studies. The process of limb regeneration can be divided into three major phases: wound healing and dedifferentiation; blastema accumulation and blastema growth; differentiation and morphogenesis (Iten and Bryant, 1973). Following amputation, the wound surface is covered rapidly by epithelial cells, which form the wound epidermis at the end of the stump. More importantly, a specialized epithelium provides signals to the underlying cells of Int. J. Dev. Biol. 59: 487-496 (2015) Abbreviations used in this paper: iTRAQ , isobaric tags for relative and absolute quantitation; IPA, ingenuity pathway analysis.

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Section: Immune Response and Cell Deathsupporting

confidence: 92%

iTRAQ-based proteomic analysis of adaptive response in the regenerating limb of the Cynops orientalis newt

Geng¹,

Guo²,

Zang³

et al. 2015

Int. J. Dev. Biol.

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“…Similar trends were also observed for the expression of other genes involved in cell cycle control (Figure 4B , middle panel, Supplementary Table S3 ). Moreover, treated samples displayed up-regulation of some transcripts related to the heat shock protein family, that recently have been suggested to be crucial in sustaining proliferation and self-renewal of stem cells [ 29 ] (Figure 4B , right panel, Supplementary Table S4 ). To validate our microarray study MCF-7 mammospheres treated with leptin were evaluated for the expression of a panel of genes by using real-time PCR (Figure 4C ).…”

Section: Resultsmentioning

confidence: 87%

Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity

et al. 2015

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Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patient-derived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan–Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSC-mediated disease progression.

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“…Similar trends were also observed for the expression of other genes involved in cell cycle control (Figure 4B, middle panel, Supplementary Table S3). Moreover, treated samples displayed up-regulation of some transcripts related to the heat shock protein family, that recently have been suggested to be crucial in sustaining proliferation and self-renewal of stem cells [29] (Figure 4B, right panel, Supplementary Table S4).…”

Section: Gene Expression Profiling In Leptin or Stromal Cm-treated Mammosphere-derived Cellsmentioning

confidence: 81%

“…Our results clearly evidenced that a number of genes involved in cell cycle control showed a similar expression profile upon treatment with stromal-CM and leptin. Another family of genes, crucial in sustaining self-renewal of stem cells [29], is the heat shock protein family. We have previously demonstrated that the HSP90, a main functional component of this chaperone complex, is a target of leptin in breast cancer cells [20].…”

Section: Discussionmentioning

confidence: 99%

Leptin as a Mediator of Tumor‐Stromal Interactions Promotes Breast Cancer Stem Cell Activity.

Catalano¹,

Giordano²,

Panza³

et al. 2015

The FASEB Journal

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Breast cancer stem cells (BCSCs) play crucial roles in tumor initiation, metastasis and therapeutic resistance. A strict dependency between BCSCs and stromal cell components of tumor microenvironment exists. Thus, novel therapeutic strategies aimed to target the crosstalk between activated microenvironment and BCSCs have the potential to improve clinical outcome. Here, we investigated how leptin, as a mediator of tumor-stromal interactions, may affect BCSC activity using patientderived samples (n = 16) and breast cancer cell lines, and determined the potential benefit of targeting leptin signaling in these model systems. Conditioned media (CM) from cancer-associated fibroblasts and breast adipocytes significantly increased mammosphere formation in breast cancer cells and depletion of leptin from CM completely abrogated this effect. Mammosphere cultures exhibited increased leptin receptor (OBR) expression and leptin exposure enhanced mammosphere formation. Microarray analyses revealed a similar expression profile of genes involved in stem cell biology among mammospheres treated with CM and leptin. Interestingly, leptin increased mammosphere formation in metastatic breast cancers and expression of OBR as well as HSP90, a target of leptin signaling, were directly correlated with mammosphere formation in metastatic samples (r = 0.68/p = 0.05; r = 0.71/p = 0.036, respectively). Kaplan-Meier survival curves indicated that OBR and HSP90 expression were associated with reduced overall survival in breast cancer patients (HR = 1.9/p = 0.022; HR = 2.2/p = 0.00017, respectively). Furthermore, blocking leptin signaling by using a full leptin receptor antagonist significantly reduced Oncotarget 1263 www.impactjournals.com/oncotarget mammosphere formation in breast cancer cell lines and patient-derived samples. Our results suggest that leptin/leptin receptor signaling may represent a potential therapeutic target that can block the stromal-tumor interactions driving BCSCmediated disease progression.

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Stem cell protection mechanisms in planarians: the role of some heat shock genes

Cited by 13 publications

References 44 publications

iTRAQ-based proteomic analysis of adaptive response in the regenerating limb of the Cynops orientalis newt

iTRAQ-based proteomic analysis of adaptive response in the regenerating limb of the Cynops orientalis newt

Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity

Leptin as a Mediator of Tumor‐Stromal Interactions Promotes Breast Cancer Stem Cell Activity.

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