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Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells.

ABSTRACT: Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12-interacting protein. Fibulins are components of basement membranes and elastic matrix fibers in connective tissue. Besides this structural function, fibulins also play crucial roles in different biological events, including tumorigenesis. To examine the functional consequences of the ADAMTS-12/fibulin-2 interaction, we performed different in vitro assays using two breast cancer cell lines: the poorly invasive MCF-7 and the highly invasive MDA-MB-231. Overall our data indicate that this interaction promotes anti-tumor effects in breast cancer cells. To assess the in vivo relevance of this interaction, we induced tumors in nude mice using MCF-7 cells expressing both ADAMTS-12 and fibulin-2 that showed a remarkable growth deficiency. Additionally, we also found that ADAMTS-12 may elicit pro-tumor effects in the absence of fibulin-2. Immunohistochemical staining of breast cancer samples allowed the detection of both ADAMTS-12 and fibulin-2 in the connective tissue surrounding tumor area in less aggressive carcinomas. However, both proteins are hardly detected in more aggressive tumors. These data and survival analysis plots of breast cancer patients suggest that concomitant detection of ADAMTS-12 and fibulin-2 could be a good prognosis marker in breast cancer diagnosis.

SUBMITTER: Fontanil T

PROVIDER: S-EPMC4012729 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells.

Fontanil Tania T Rúa Susana S Llamazares María M Moncada-Pazos Angela A Quirós Pedro M PM García-Suárez Olivia O Vega Jose A JA Sasaki Takako T Mohamedi Yamina Y Esteban Manuel M MM Obaya Alvaro J AJ Cal Santiago S

Oncotarget 20140301 5

Balance between pro-tumor and anti-tumor effects may be affected by molecular interactions within tumor microenvironment. On this basis we searched for molecular partners of ADAMTS-12, a secreted metalloprotease that shows both oncogenic and tumor-suppressive effects. Using its spacer region as a bait in a yeast two-hybrid screen, we identified fibulin-2 as a potential ADAMTS-12-interacting protein. Fibulins are components of basement membranes and elastic matrix fibers in connective tissue. Bes ...[more]

PMID: 24457941

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Project description:PURPOSE:Whether the benefits of exercise during chemotherapy continue into survivorship is not well-known. Here, the aim was to examine the effects of two exercise interventions on self-reported health-related and objectively measured physiological outcomes 12 months following commencement of chemotherapy. METHODS:Two hundred and forty women with breast cancer stage I-IIIa were randomized to 16 weeks of high-intensity aerobic interval training combined with either resistance training (RT-HIIT), or moderate-intensity aerobic training (AT-HIIT), or to usual care (UC). PRIMARY OUTCOME:cancer-related fatigue (CRF); secondary outcomes: quality of life (QoL), symptom burden, muscle strength, cardiorespiratory-fitness, body mass, and return to work. RESULTS:Compared to UC, both RT-HIIT and AT-HIIT significantly counteracted increases in total CRF (ES = - 0.34; ES = - 0.10), daily life CRF (ES=-0.76; ES=-0.50, and affective CRF (ES=-0.60; ES=-0.39). Both RT-HIIT and AT-HIIT reported significantly lower total symptoms (ES = - 0.46, ES = - 0.46), and displayed gains in lower limb (ES = 0.73; ES = 1.03) and handgrip muscle strength (surgery side ES = 0.70, ES = 0.71; non-surgery side ES = 0.57, ES = 0.59). AT-HIIT displayed significant reductions in body mass (ES = - 0.24), improved QoL: role (ES = 0.33) and emotional functioning (ES = 0.40), and a larger proportion had returned to work (p = 0.02) vs UC. CONCLUSION:These findings emphasize the beneficial effects of supervised high-intensity exercise during chemotherapy to improve the health and to reduce societal costs associated with prolonged sick leave for patients with breast cancer several months following chemotherapy. IMPLICATIONS FOR CANCER SURVIVORS:These findings provide important information with substantial positive consequences for breast cancer survivorship. High-intensity exercise programs during chemotherapy and support to maintain physical activity can be a powerful strategy to manage or prevent many of the short- and long-term adverse effects of treatment for the increasing cohort of cancer survivors.

Dataset Information

Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells.

Publications

Interaction between the ADAMTS-12 metalloprotease and fibulin-2 induces tumor-suppressive effects in breast cancer cells.

Similar Datasets

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