Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: Implications for bone marrow metastasis

Singh, Deeppreet; Joshi, Deval D.; Hameed, Meera; Qian, Jing; Gascón, Pedro; Maloof, Paul; Mosenthal, Anne C.; Rameshwar, Pranela

doi:10.1073/pnas.97.1.388

Cited by 150 publications

(200 citation statements)

References 39 publications

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“…For example, PPT-I is overexpressed in breast and other endocrine cancers, and the high levels of PPT-I peptides appear to be involved in autocrine proliferation of the cancer cells (4). In fact, overexpression of the inducible repressor, ICERII␥, in endocrine and neuroendocrine cancers alters the growth of these tumors (30).…”

Section: Discussionmentioning

confidence: 99%

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Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Qian¹,

Yehia

Molina

et al. 2001

The Journal of Immunology

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Preprotachykinin-I gene (PPT-I) encodes several peptides with organ-specific functions that link the neuroendocrine-immune-hemopoietic axis. We cloned upstream of the initiation site of human PPT-I promoter and identified consensus sequences for two cAMP response elements (CRE). PPT-I is induced by cytokines including those that signal through the cAMP pathway. Therefore, we studied the role of the two CRE in IL-1α and stem cell factor (SCF) stimulation of bone marrow stroma because both cytokines induce endogenous PPT-I in these cells and activate the cAMP pathway. Furthermore, bone marrow stroma expresses the transcription factors regulated by the cAMP pathways such as the repressor (ICERIIγ) and activator (CREMτ). Mutagenesis of the two CRE and/or cotransfection with vectors that express ICERIIγ or CREMτ indicated that the two CRE have major roles in PPT-I expression. The two CRE are also required for optimal promoter activity by SCF and IL-1α. A particular cytokine could concomitantly induce PPT-I and the high affinity G protein-coupled receptor for PPT-I peptides, NK-1R. We showed that SCF, a representative cytokine, induced PPT-I and NK-1R leading to autocrine and/or paracrine cell activation. Because NK-1R activates cAMP through the G protein, the results suggest that the presence of CRE sequences within PPT-I promoter could be important in the regulation of PPT-I expression by cytokines, irrespective of their ability to signal through cAMP. As PPT-I is implicated in hemopoietic regulation, immune responses, breast cancer, and other neural functions, these studies add to the basic biology of these processes and could provide targets for drug development.

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Section: Discussionmentioning

confidence: 99%

“…Quantitative RT-PCR with total RNA extracted from BM stroma and construction of standard DNA were previously described (4). The end sequences of the standard DNA contained gene-specific sequences that are complementary for the reaction primers.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Qian¹,

Yehia

Molina

et al. 2001

The Journal of Immunology

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“…(a) by inhibiting tumor cell proliferation in several tumor cell lines, including breast cancer cells [10,13,14]. NK-1 receptor antagonists induce cellular death by apoptosis [10,14]; (b) by inhibiting tumor neoangiogenesis [15]; and (c) by inhibiting the migration of tumoral cells (e.g., breast carcinoma cells) [9,16].…”

Section: Nk-1 Receptor Antagonists Exert An Antitumor Actionmentioning

confidence: 99%

“…3. The presence of both SP [11] and NK-1 receptors in tumoral tissues, including breast carcinoma [10,12,13], has been demonstrated. This means that SP could act through an autocrine mechanism, through which SP is secreted from primary tumors.…”

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Paravertebral anesthesia: how substance P and the NK-1 receptor could be involved in regional block and breast cancer recurrence

Muñoz

Rosso

Casinello

et al. 2010

Breast Cancer Res Treat

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Neuropeptides in Cancer: Friend and Foe?

Berisha

Borniger

2022

Advanced Biology

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highly dynamic network of various cell types (e.g., cancer cells, endothelial cells, immune cells, fibroblasts) that exert differential effects on neuronal activity within the local environment. Thus, complex signaling between cancer and stromal cells in the TME results in altered firing rates of local nerves. Reciprocally, increased neuronal activity and subsequent release of classical neurotransmitters and/or neuropeptides within the TME results in enhanced cancer progression and subsequent metastasis in various preclinical models and clinical studies. [5][6][7][8][9] Nerves interact with multiple stromal cells in the TME where they indirectly promote tumor growth, progression, and subsequent metastasis. [10] Several studies have demonstrated that sympathetic nerve innervation and subsequent release of the neurotransmitter norepinephrine (NE) is increased in breast tumors. [6,8,9] However, recent work has demonstrated that there is an inverse relationship between tumor weight and norepinephrine content (i.e., larger the size of the tumor, the lower the levels of NE), despite increased innervation of sympathetic nerves within the TME. [11] These findings may be attributed to a relatively unexplored phenomenon: neuropeptide release within the TME. Neuropeptides are molecular messengers that regulate a variety of functions in the central and peripheral nervous systems via binding G-protein-coupled receptors (GPCRs) on target cells. One of the many functions of neuropeptides is serving as growth factors for normal cells via the activation of the heterotrimeric G protein Gq and subsequent synthesis of second messengers and engagement of tyrosine phosphorylation cascades. Neuropeptides act as neuromodulators, in that they can alter the response of neurons to neurotransmitters and other circulating signals, such as leptin, ghrelin, glucose, and insulin-all of which are affected during cancer progression. [12][13][14][15][16][17] For example, both neuropeptide Y (NPY) and hypocretin/orexin neurons appear to mediate some of the orexigenic effects of centrally administered ghrelin as administration of NPY receptor antagonists attenuated ghrelininduced feeding. Similarly, ghrelin-induced feeding was suppressed in orexin knockout mice, indicating that ghrelin may stimulate feeding through both the orexin and NPY systems. [18] However, neuropeptide signaling is exploited within cancer cells and many studies demonstrate the contribution of neuropeptides in tumor cell proliferation and migration, [19] with many major neuropeptides also potentially contributing to cancer processes (see Table 1). Additionally, neuropeptides exert direct Neuropeptides are small regulatory molecules found throughout the body, most notably in the nervous, cardiovascular, and gastrointestinal systems. They serve as neurotransmitters or hormones in the regulation of diverse physiological processes. Cancer cells escape normal growth control mechanisms by altering their expression of growth factors, receptors, or intracellular signals, and neuropeptid...

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Increased expression of preprotachykinin-I and neurokinin receptors in human breast cancer cells: Implications for bone marrow metastasis

Cited by 150 publications

References 39 publications

Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Cloning of Human Preprotachykinin-I Promoter and the Role of Cyclic Adenosine 5′-Monophosphate Response Elements in Its Expression by IL-1 and Stem Cell Factor

Paravertebral anesthesia: how substance P and the NK-1 receptor could be involved in regional block and breast cancer recurrence

Neuropeptides in Cancer: Friend and Foe?

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