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Inflammation and tumor microenvironment in lymph node metastasis.

Wu X, Takekoshi T, Sullivan A, Hwang ST - Cancers (Basel) (2011)

Bottom Line: In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis).Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites.These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. sthwang@mcw.edu.

ABSTRACT
In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis). Herein, principally reviewing experimental and clinical data related to malignant melanoma, we discuss diverse factors that are mechanistically involved in LN metastasis. We highlight recent data that link tumor microenvironment, including inflammation (at the cellular and cytokine levels) and tumor-induced lymphangiogenesis, with nodal metastasis. Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites. These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers.

No MeSH data available.


Related in: MedlinePlus

CCR7 facilitated B16 cell tumor formation and lymph node (LN) metastasis following ear skin inoculation. (A). Contrary to control mice injected with pLNCX2-B16, the mice inoculated with CCR7-B16 cells developed ear tumors within three weeks, which were accompanied by cervical LN metastasis in 90% of mice at Day 20; (B). Kinetics of B16 tumor growth in ears showed that CCR7 expression enhanced tumorigenesis in primary sites in addition to facilitating LN metastasis. (Inoculation number: 100,000 cells/ear) [48].
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f1-cancers-03-00927: CCR7 facilitated B16 cell tumor formation and lymph node (LN) metastasis following ear skin inoculation. (A). Contrary to control mice injected with pLNCX2-B16, the mice inoculated with CCR7-B16 cells developed ear tumors within three weeks, which were accompanied by cervical LN metastasis in 90% of mice at Day 20; (B). Kinetics of B16 tumor growth in ears showed that CCR7 expression enhanced tumorigenesis in primary sites in addition to facilitating LN metastasis. (Inoculation number: 100,000 cells/ear) [48].

Mentions: When limited numbers of tumor cells were inoculated into murine skin, overexpression of CCR7 directly facilitated primary tumor formation (Figure 1) [48]. In the studies by Fang et al., immunological rejection of non-CCR7-expressing B16 melanoma cells was apparent within the first week of tumor implantation, suggesting the CCR7 expression can help tumor cells evade host antitumor responses. Expression levels of interferon-regulated chemokines such as CXCL10 (as well as numbers of CD4+ and CD8+ T cells) were 5-10 fold lower in the CCR7-B16 tumors compared to the control tumors, suggesting that expression of CCR7 was able to dampen the anti-tumor immune responses within the tumor microenvironment. Careful serial comparative analysis of numbers of metastatic cells in the draining LN of mice injected with either CCR7- or control B16 cells showed that significant differences in numbers of metastatic B16 cells did not occur until 14 days or more after inoculation when CCR7-B16 tumors were grossly visible [48]. These data suggested that CCR7 does not immediately enhance LN migration of CCR7-bearing cells. Alternatively, it is possible that the small numbers of tumor cells that do migrate to draining LN in both cases are localized within different regions of the LN, possibly affecting anti-tumor response.


Inflammation and tumor microenvironment in lymph node metastasis.

Wu X, Takekoshi T, Sullivan A, Hwang ST - Cancers (Basel) (2011)

CCR7 facilitated B16 cell tumor formation and lymph node (LN) metastasis following ear skin inoculation. (A). Contrary to control mice injected with pLNCX2-B16, the mice inoculated with CCR7-B16 cells developed ear tumors within three weeks, which were accompanied by cervical LN metastasis in 90% of mice at Day 20; (B). Kinetics of B16 tumor growth in ears showed that CCR7 expression enhanced tumorigenesis in primary sites in addition to facilitating LN metastasis. (Inoculation number: 100,000 cells/ear) [48].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756397&req=5

f1-cancers-03-00927: CCR7 facilitated B16 cell tumor formation and lymph node (LN) metastasis following ear skin inoculation. (A). Contrary to control mice injected with pLNCX2-B16, the mice inoculated with CCR7-B16 cells developed ear tumors within three weeks, which were accompanied by cervical LN metastasis in 90% of mice at Day 20; (B). Kinetics of B16 tumor growth in ears showed that CCR7 expression enhanced tumorigenesis in primary sites in addition to facilitating LN metastasis. (Inoculation number: 100,000 cells/ear) [48].
Mentions: When limited numbers of tumor cells were inoculated into murine skin, overexpression of CCR7 directly facilitated primary tumor formation (Figure 1) [48]. In the studies by Fang et al., immunological rejection of non-CCR7-expressing B16 melanoma cells was apparent within the first week of tumor implantation, suggesting the CCR7 expression can help tumor cells evade host antitumor responses. Expression levels of interferon-regulated chemokines such as CXCL10 (as well as numbers of CD4+ and CD8+ T cells) were 5-10 fold lower in the CCR7-B16 tumors compared to the control tumors, suggesting that expression of CCR7 was able to dampen the anti-tumor immune responses within the tumor microenvironment. Careful serial comparative analysis of numbers of metastatic cells in the draining LN of mice injected with either CCR7- or control B16 cells showed that significant differences in numbers of metastatic B16 cells did not occur until 14 days or more after inoculation when CCR7-B16 tumors were grossly visible [48]. These data suggested that CCR7 does not immediately enhance LN migration of CCR7-bearing cells. Alternatively, it is possible that the small numbers of tumor cells that do migrate to draining LN in both cases are localized within different regions of the LN, possibly affecting anti-tumor response.

Bottom Line: In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis).Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites.These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. sthwang@mcw.edu.

ABSTRACT
In nearly all human cancers, the presence of lymph node (LN) metastasis increases clinical staging and portends worse prognosis (compared to patients without LN metastasis). Herein, principally reviewing experimental and clinical data related to malignant melanoma, we discuss diverse factors that are mechanistically involved in LN metastasis. We highlight recent data that link tumor microenvironment, including inflammation (at the cellular and cytokine levels) and tumor-induced lymphangiogenesis, with nodal metastasis. Many of the newly identified genes that appear to influence LN metastasis facilitate general motility, chemotactic, or invasive properties that also increase the ability of cancer cells to disseminate and survive at distant organ sites. These new biomarkers will help predict clinical outcome and point to novel future therapies in metastatic melanoma as well as other cancers.

No MeSH data available.


Related in: MedlinePlus