Monocyte-Fibronectin Interactions, Via α5β1 Integrin, Induce Expression of CXC Chemokine-Dependent Angiogenic Activity

White, Eric S.; Livant, Donna L.; Markwart, Sonja

doi:10.4049/jimmunol.167.9.5362

Cited by 34 publications

(31 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Potential mediators of SPARC signaling are cell surface integrins. In that respect, integrin activation by fibronectin induced IL-8 and GRO expressions in melanoma cells and monocytes (32,33). In addition, integrins modulate leukotriene production and secretion by neutrophils (34).…”

Section: Resultsmentioning

confidence: 99%

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

et al. 2005

View full text Add to dashboard Cite

The expression of secreted protein acidic and rich in cysteine (SPARC) has been associated with the malignant progression of different types of human cancer. SPARC was associated with tumor cell capacity to migrate and invade, although its precise role in tumor progression is still elusive. In the present study, we show that SPARC produced by melanoma cells modulates the antitumor activity of polymorphonuclear leukocytes (PMN). Administration to nude mice of human melanoma cells in which SPARC expression was transiently or stably knocked down by antisense RNA (SPARC-sup cells) promoted PMN recruitment and obliterated tumor growth even when SPARC-sup cells accounted for only 10% of injected malignant cells. In addition, SPARC-sup cells stimulated the in vitro migration and triggered the antimelanoma cytotoxic capacity of human PMN, an effect that was reverted in the presence of SPARC purified from melanoma cells or by reexpressing SPARC in SPARC-sup cells. Leukotrienes, interleukin 8, and growth-related oncogene, in combination with Fas ligand and interleukin 1, mediated SPARC effects. These data indicate that SPARC plays an essential role in tumor evasion from immune surveillance through the inhibition of the antitumor PMN activity. (Cancer Res 2005; 65(12): 5123-32)

show abstract

Section: Resultsmentioning

confidence: 99%

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

et al. 2005

View full text Add to dashboard Cite

show abstract

“…In addition to functioning in cellular adhesion to the extracellular matrix, integrins are known to mediate many diverse processes involving cell migration and invasion. For example, the ␣ 5 ␤ 1 fibronectin receptor has been shown to play a key role in wound healing by mediating invasion of the provisional matrix by fibroblasts, endothelial cells, and keratinocytes to accomplish angiogenesis and re-epithelialization (3,4). Also, integrins have been shown to function in the progression of a variety of cancers (reviewed in ref.…”

Section: Introductionmentioning

confidence: 99%

Integrin Fibronectin Receptors in Matrix Metalloproteinase-1–Dependent Invasion by Breast Cancer and Mammary Epithelial Cells

et al. 2004

Self Cite

View full text Add to dashboard Cite

Integrins contribute to progression in many cancers, including breast cancer. For example, the interaction of ␣ 5 ␤ 1 with plasma fibronectin causes the constitutive invasiveness of human prostate cancer cells. Inhibition of this process reduces tumorigenesis and prevents metastasis and recurrence. In this study, naturally serum-free basement membranes were used as invasion substrates. Immunoassays were used to compare the roles of

show abstract

“…A similar amino acid sequence on fibronectin (PHSRN), known as the synergy region, potentiates the binding of fibronectin to ␣ 5 ␤ 1 , and ATN-161 acts by interfering with this interaction. A study from White et al 18 demonstrated that the PHSCN peptide may inhibit expression of pro-angiogenic CXC chemokines by monocytes that had been plated on fibronectin. Recent studies have shown that ATN-161 interacts with the N-terminus of the ␤ 1 -domain of integrin ␣ 5 ␤ 1 , which may lock this integrin in an inactive conformation (Parry and Mazar, unpublished data, 2001).…”

mentioning

confidence: 99%

Inhibition of integrin α₅β₁ function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice

Stoeltzing

Liu

Reinmuth

et al. 2003

Intl Journal of Cancer

206

150

View full text Add to dashboard Cite

Integrin ␣ 5 ␤ 1 is expressed on activated endothelial cells and plays a critical role in tumor angiogenesis. We hypothesized that a novel integrin ␣ 5 ␤ 1 antagonist, ATN-161, would inhibit angiogenesis and growth of liver metastases in a murine model. We further hypothesized that combining ATN-161 with 5-fluorouracil (5-FU) chemotherapy would enhance the antineoplastic effect. Murine colon cancer cells (CT26) were injected into spleens of BALB/c mice to produce liver metastases. Four days thereafter, mice were given either ATN-161 (100 mg/kg, every 3rd day) or saline by intraperitoneal injection, with or without combination of continuousinfusion 5-FU (100 mg/kg/2 weeks), which was started on day 7. On day 20 after tumor cell inoculation, mice were killed and liver weights and number of liver metastases were determined. A follow-up study on survival was also conducted in which mice were randomized to receive ATN- Key words: angiogenesis; colon cancer; integrins; liver metastasesIntegrins are heterodimeric transmembrane glycoproteins that mediate their own function upon binding to components of the extracellular matrix such as fibronectin, vitronectin and collagen. Integrins are composed of various ␣-and ␤-subunits that form the receptor (reviewed in reference 1), and the unique dimer compositions determine the ability to bind to specific ligands.Integrins regulate cell adhesion and are expressed on the surface of many cell types, including tumor cells, ECs and numerous nonmalignant cell types. 2 In addition to their role in cell adhesion, integrins have been shown to affect intracellular signaling processes and thereby regulate cell survival and proliferation. 2-4 Recently, specific integrins have been identified as being crucial for mediating the angiogenic response of endothelial cells to angiogenic growth factors such as VEGF and bFGF. The integrins ␣ V ␤ 3 , ␣ V ␤ 5 and ␣ 5 ␤ 1 have been shown to play important roles in neoplastic and non-neoplastic angiogenesis by promoting EC migration, proliferation and survival. 5-8 Therefore, endothelial-specific integrins have become a promising target for anti-angiogenic approaches in antineoplastic regimens and in the treatment of nonmalignant angiogenic disorders. 9 -12 The integrin ␣ 5 ␤ 1 is of particular interest as a target since amounts of this integrin and its ligand fibronectin are significantly increased on tumor vessels of many solid malignancies. 13 In some types of cancer, integrin ␣ 5 ␤ 1 is also expressed on tumor cells and plays a direct role in tumor cell migration, invasion, and survival. 14,15 In colorectal cancers, ␣ 5 ␤ 1 overexpression has been associated with invasiveness and malignant progression. 14 However, only a few human colon cancer cell lines are known to express this integrin. 14,16,17 Recently, Livant et al. 15 demonstrated that a small peptide antagonist (amino-acid sequence PHSCN) to integrin ␣ 5 ␤ 1 significantly reduced neovascularization and formation of metastases in an animal model of prostate carcinoma that expresses integr...

show abstract

Monocyte-Fibronectin Interactions, Via α5β1 Integrin, Induce Expression of CXC Chemokine-Dependent Angiogenic Activity

Cited by 34 publications

References 31 publications

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

Integrin Fibronectin Receptors in Matrix Metalloproteinase-1–Dependent Invasion by Breast Cancer and Mammary Epithelial Cells

Inhibition of integrin α₅β₁ function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice

Contact Info

Product

Resources

About

Monocyte-Fibronectin Interactions, Via α5β1 Integrin, Induce Expression of CXC Chemokine-Dependent Angiogenic Activity

Cited by 34 publications

References 31 publications

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

Secreted Protein Acidic and Rich in Cysteine Produced by Human Melanoma Cells Modulates Polymorphonuclear Leukocyte Recruitment and Antitumor Cytotoxic Capacity

Integrin Fibronectin Receptors in Matrix Metalloproteinase-1–Dependent Invasion by Breast Cancer and Mammary Epithelial Cells

Inhibition of integrin α5β1 function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice

Contact Info

Product

Resources

About

Inhibition of integrin α₅β₁ function with a small peptide (ATN‐161) plus continuous 5‐FU infusion reduces colorectal liver metastases and improves survival in mice