Matricellular proteins and inflammatory cells: A task force to promote or defeat cancer?

Llera, Andrea S.; Girotti, María Romina; Benedetti, Lorena; Podhajcer, Osvaldo L.

doi:10.1016/j.cytogfr.2009.11.010

Cited by 14 publications

(11 citation statements)

References 135 publications

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“…CAF have the paradoxical role of attacking tumors while at the same time supporting them by expressing soluble and membrane molecules, including cytokines and chemokines (26,27). The final set of candidate cells that may have activated inflammation amplifiers is endothelial cells.…”

Section: Future Directionsmentioning

confidence: 99%

Inflammation Amplifier, a New Paradigm in Cancer Biology

Atsumi

Singh²,

Sabharwal³

et al. 2014

Cancer Research

183

146

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Tumor-associated inflammation can induce various molecules expressed from the tumors themselves or surrounding cells to create a microenvironment that potentially promotes cancer development. Inflammation, particularly chronic inflammation, is often linked to cancer development, even though its evolutionary role should impair nonself objects including tumors. The inflammation amplifier, a hyperinducer of chemokines in nonimmune cells, is the principal machinery for inflammation and is activated by the simultaneous stimulation of NF-kB and STAT3. We have redefined inflammation as local activation of the inflammation amplifier, which causes an accumulation of various immune cells followed by dysregulation of local homeostasis. Genes related to the inflammation amplifier have been genetically associated with various human inflammatory diseases. Here, we describe how cancer-associated genes, including interleukin (IL)-6, Ptgs2, ErbB1, Gas1, Serpine1, cMyc, and Vegfa, are strongly enriched in genes related to the amplifier. The inflammation amplifier is activated by the stimulation of cytokines, such as TNF-a, IL-17, and IL-6, resulting in the subsequent expression of various target genes for chemokines and tumor-related genes like BCL2L11, CPNE7, FAS, HIF1-a, IL-1RAP, and SOD2. Thus, we conclude that inflammation does indeed associate with the development of cancer. The identified genes associated with the inflammation amplifier may thus make potential therapeutic targets of cancers. Cancer Res; 74(1);

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Section: Future Directionsmentioning

confidence: 99%

Inflammation Amplifier, a New Paradigm in Cancer Biology

Atsumi

Singh²,

Sabharwal³

et al. 2014

Cancer Research

183

146

View full text Add to dashboard Cite

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“…Anoikis resistance is also required for cancer cell survival while traveling through the lymphatic and circulatory systems into the secondary tissue sites [157]. Circulating tumor cells also devise immunosuppressive strategies to avoid patrolling innate immune cells, such as natural killer cells, macrophages, or adaptive immune responses involving B and T lymphocytes [158]. These immunosuppressive strategies would increase tumor tolerance against immune responses and improve their survival capabilities.…”

Section: Evade Immune Surveillance and Anoikis Resistancementioning

confidence: 99%

“…Metastatic tumors are characterized by the overproduction of several matricellular proteins that are believed to play a key role in more advanced steps of tumor progression, such as tumor induced angiogenesis, the inhibition of infiltrating immune cells and the protection of disseminated tumor cells in circulation [156, 158, 159]. An increase in SPARC activity is associated with diminished immune surveillance during tumorigenesis [160].…”

Section: Evade Immune Surveillance and Anoikis Resistancementioning

confidence: 99%

Matricellular Proteins: A Sticky Affair with Cancers

Chong

Tan

Huang

et al. 2012

Journal of Oncology

114

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The multistep process of metastasis is a major hallmark of cancer progression involving the cointeraction and coevolution of the tumor and its microenvironment. In the tumor microenvironment, tumor cells and the surrounding stromal cells aberrantly secrete matricellular proteins, which are a family of nonstructural proteins in the extracellular matrix (ECM) that exert regulatory roles via a variety of molecular mechanisms. Matricellular proteins provide signals that support tumorigenic activities characteristic of the metastastic cascade such as epithelial-to-mesenchymal (EMT) transition, angiogenesis, tumor cell motility, proliferation, invasion, evasion from immune surveillance, and survival of anoikis. Herein, we review the current understanding of the following matricellular proteins and highlight their pivotal and multifacted roles in metastatic progression: angiopoietin-like protein 4 (ANGPTL4), CCN family members cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) and CCN6, osteopontin (OPN), secreted protein acidic and rich in cysteine (SPARC), tenascin C (TNC), and thrombospondin-1 and -2 (TSP1, TSP2). Insights into the signaling mechanisms resulting from the interaction of these matricellular proteins and their respective molecular partner(s), as well as their subsequent contribution to tumor metastasis, are discussed. In addition, emerging evidences of their promising potential as therapeutic options and/or targets in the treatment of cancer are also highlighted.

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“…In addition to immune editing, the immune system has been shown to play a role in regulating the tumor microenvironment through programs of inflammation and/or wound healing [60,63,64]. Immune effectors have been shown to be integral to both the initiation and restraint of tumorigenesis [65].…”

Section: Oncogene Addiction and The Host Immune Systemmentioning

confidence: 99%

Noncanonical roles of the immune system in eliciting oncogene addiction

Casey

Bellovin

Felsher

2013

Current Opinion in Immunology

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Summary Cancer is highly complex. The magnitude of this complexity makes it highly surprising that even the brief suppression of an oncogene can sometimes result in rapid and sustained tumor regression illustrating that cancers can be “oncogene addicted” [1-10]. The essential implication is that oncogenes may not only fuel the initiation of tumorigenesis, but in some cases necessarily their surfeit of activation is paramaount to maintain a neoplastic state [11]. Oncogene suppression acutely restores normal physiological programs that effectively overrides secondary genetic events and a cancer collapses [12,13]. Oncogene addiction is mediated both through both tumor intrinsic cell-autonomous mechanisms including proliferative arrest, apoptosis, differentiation and cellular senescence [1,2,4,12] but also host-dependent mechanisms that interact with these tumor intrinsic programs [14,15]. Notably, oncogene inactivation elicits a host immune response that involves specific immune effectors and cytokines that facilitate a remodeling of the tumor microenvironment including the shut down of angiogenesis and the induction of cellular senescence of tumor cells [16]. Hence, immune effectors are critically involved in tumor initiation and prevention [17-19] and progression [20], but also appear to be essential to tumor regression upon oncogene inactivation [21-23]. The understanding how the inactivation of an oncogene elicits a systemic signal in the host that prompts a deconstruction of a tumor could have important implications. The combination of oncogene-targeted therapy together with immunomodulatory therapy may be ideal for the development of both a robust tumor intrinsic as well as immunological effectively leading to sustained tumor regression.

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Matricellular proteins and inflammatory cells: A task force to promote or defeat cancer?

Cited by 14 publications

References 135 publications

Inflammation Amplifier, a New Paradigm in Cancer Biology

Inflammation Amplifier, a New Paradigm in Cancer Biology

Matricellular Proteins: A Sticky Affair with Cancers

Noncanonical roles of the immune system in eliciting oncogene addiction

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