Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells

Flageole, Hélène; Senterman, Mary K.; Trudel, Judith L.

doi:10.1016/0022-4804(92)90088-h

Cited by 28 publications

(19 citation statements)

References 17 publications

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“…Its action on the cancer cells appears to be autocrine since NK1 antagonist has been shown to mediate anti-tumor activity (Rosso et al, 2008). On the other hand, Substance P also enhances the expansion of lymphokine-activated killer cells against colon cancer cells (Flageole et al, 1992). These two properties of substance P appear paradoxical.…”

Section: Colon Cancermentioning

confidence: 76%

TAC1 (tachykinin, precursor 1)

Lim¹,

Sa²,

Rameshwar³

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Section: Colon Cancermentioning

confidence: 76%

TAC1 (tachykinin, precursor 1)

Lim¹,

Sa²,

Rameshwar³

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…Studies indicate, however, that the effect of SP is dependent on the tumor model in which it is examined. While, in some models, SP has been found to stimulate tumor growth, other studies have documented the opposite effect (6)(7)(8)(9)(10)(11)(12)(13)(14)(28)(29)(30)(31). For example, it has been demonstrated that pre-treatment of mice with SP protects against melanoma growth by inducing anti-tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, silencing of the SP gene has been implicated in colon carcinogenesis (6,32). Flageole et al reported that SP increases the cytotoxic immune response to colorectal cancer cells (12). SP has also been shown to supress the motility of cancer cells, decreasing invasiveness in prostate cancer (14).…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, we observed that the depletion of SP from sensory nerve endings increased breast cancer metastases (4,5). Furthermore, treatment with SP decreased the growth of melanomas, small-cell lung cancer, colon cancer and prostate cancer (6)(7)(8)(9)(10)(11)(12)(13)(14). The role of SP during metastatic growth is therefore controversial, and requires further study.…”

Section: Introductionmentioning

confidence: 99%

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Radiotherapy-induced decreases in substance P levels may potentiate melanoma growth

Erin¹

2009

Mol Med Rep

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Abstract. Substance P, a member of the tachykinin family, is expressed in primary invasive malignant melanomas, metastatic melanomas, melanomas in situ, atypical naevi, and spindle and epithelioid cell naevi. The role of substance P in cancer development and progression is not clear. Radiotherapy, which is used extensively in the treatment of malignancies, alters substance P levels. It is, however, not known whether radiotherapy affects substance P levels in melanomas or in the tumor microenvironment. Given the fact that melanomas express substance P, possible radiation-induced changes in substance P content may underlie their radio-resistance. Hence, the aim of the present study was to determine the effects of radiotherapy on the growth of B16F10 melanomas as well as on the tumor and systemic expression of substance P. In vivo exposure of tumor-bearing C5BL/6 mice to ionizing radiation (45 Gy administered in three fractions) arrested tumor growth for three weeks and induced 3-fold increases in survival, as well as decreasing substance P levels in primary tumors and the surrounding skin. Although radiotherapy was applied locally (1 x 1 cm) at the mid-flank region of the animal, it also induced systemic changes in the levels of substance P. Specifically, radiotherapy decreased substance P levels in skin distant from the radiation field as well as in the lungs and adrenals. In order to understand the significance of this effect, B16F10 cells and cells made from metastatic lesions (B16LNAD cells) were treated with substance P. Substance P inhibited the growth of B16F10 and B16LNAD cells and further potentiated the inhibitory effects of radiotherapy. These findings demonstrate for the first time that substance P inhibits melanoma growth, and that radiotherapy-induced decreases in substance P levels may underlie the radio-resistance of melanomas.

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“…It has been shown that several amidated regulatory peptides, including substance P, cholecystokinin 8 (CCK8), and vasoactive inhibitory peptide (VIP), among others, regulate the growth and differentiation of T-lymphocytes (Flageole et al 1992;Ottaway 1992;Anton et al 1993;Tang et al 1993). It is possible that some of these substances and others are secreted by the thymic stromal cells as a component of the specific microenvironment, and therefore thymic epithelial cells require the amidating machinery to complete the maturation of the regulatory peptides.…”

Section: Figurementioning

confidence: 99%

Peptide-amidating Enzymes Are Expressed in the Stellate Epithelial Cells of the Thymic Medulla

Martı́nez

Farr

Vos

et al. 1998

J Histochem Cytochem.

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SUMMARY C-terminal amidation is a post-translational processing step necessary to convey biological activity to a large number of regulatory peptides. In this study we have demonstrated that the peptidyl-glycine ␣ -amidating monooxygenase enzyme complex (PAM) responsible for this activity is located in the medullary stellate epithelial cells of the thymus and in cultured epithelial cells bearing a medullary phenotype, using Northern blot, immunocytochemistry, in situ hybridization, and enzyme assays. Immunocytochemical localization revealed a granular pattern in the cytoplasm of the stellate cells, which were also positive for cytokeratins and a B-lymphocyte-associated antigen. The presence of PAM activity in medium conditioned by thymic epithelial cell lines suggests that PAM is a secreted product of these cells. Among the four epithelial cell lines examined, there was a direct correlation between PAM activity and content of oxytocin, an amidated peptide. Taken together, these data provide convincing evidence that thymic epithelial cells have the capacity to generate amidated peptides that may influence T-cell differentiation and suggest that the amidating enzymes could play an important role in the regulation of thymic physiology.

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Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells

Abstract: A thcsis slIbmitted to the Faculty of Graduate Studies and Rcscarch in partial flllfillment of the requirements of the dcgrcc of Master of Science .

Cited by 28 publications

References 17 publications

TAC1 (tachykinin, precursor 1)

TAC1 (tachykinin, precursor 1)

Radiotherapy-induced decreases in substance P levels may potentiate melanoma growth

Peptide-amidating Enzymes Are Expressed in the Stellate Epithelial Cells of the Thymic Medulla

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